View source for Kinesin

{{short description|Eukaryotic motor protein}}
{{Use dmy dates|date=April 2022}}
[[File:KinMT Gif.gif|thumb|The kinesin dimer (red) attaches to, and moves along, microtubules (blue and green).]]
[[File:Kinesin walking.gif|thumb|[[Animation]] of kinesin "walking" on a [[microtubule]]. [[Protein domain dynamics]] can only now be seen by [[neutron spin echo]] spectroscopy.]]
A '''kinesin''' is a [[protein complex]] belonging to a class of [[motor protein]]s found in [[eukaryotic]] cells. Kinesins move along [[microtubule]] (MT) filaments and are powered by the [[hydrolysis]] of [[adenosine triphosphate]] (ATP) (thus kinesins are [[ATPase]]s, a type of enzyme). The active movement of kinesins supports several cellular functions including [[mitosis]], [[meiosis]] and transport of cellular cargo, such as in [[axonal transport]], and [[intraflagellar transport]]. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery.<ref>{{cite journal | vauthors = Berg J, Tymoczko JL, Stryer L |date=2002|title=Kinesin and Dynein Move Along Microtubules|url=https://www.ncbi.nlm.nih.gov/books/NBK22572/|archive-url=https://web.archive.org/web/20191029183544/https://www.ncbi.nlm.nih.gov/books/NBK22572/|archive-date=29 October 2019|journal=Biochemistry. 5th Edition }}</ref> This form of transport is known as [[Axonal transport#Anterograde transport|anterograde transport]]. In contrast, [[dynein]]s are motor proteins that move toward the minus end of a microtubule in [[Axonal transport#Retrograde transport|retrograde transport]].{{cn|date=May 2025}}

== Discovery ==
The first kinesins to be discovered were microtubule-based anterograde intracellular transport motors<ref name="pmid12600311">{{cite journal |vauthors=Vale RD |date=February 2003 |title=The molecular motor toolbox for intracellular transport |journal=Cell |volume=112 |issue=4 |pages=467–80 |doi=10.1016/S0092-8674(03)00111-9 |pmid=12600311 |s2cid=15100327 |doi-access=free}}</ref> in 1985, based on their motility in cytoplasm extruded from the [[Squid giant axon|giant axon of the squid]].<ref>{{cite journal | vauthors = Endow SA, Kull FJ, Liu H | title = Kinesins at a glance | journal = Journal of Cell Science | volume = 123 | issue = Pt 20 | pages = 3420–4 | date = October 2010 | pmid = 20930137 | doi = 10.1242/jcs.064113 | pmc = 2951464 | doi-access = free }}</ref>

The founding member of this superfamily, kinesin-1, was isolated as a [[protein trimer|heterotetrameric]] fast axonal organelle transport motor consisting of four parts: two identical motor subunits (called Kinesin Heavy Chain (KHC) molecules) and two other molecules each known as a Kinesin Light Chain (KLC).  These were discovered via microtubule affinity purification from neuronal cell extracts.<ref name="pmid3926325">{{cite journal | vauthors = Vale RD, Reese TS, Sheetz MP | title = Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility | journal = Cell | volume = 42 | issue = 1 | pages = 39–50 | date = August 1985 | pmid = 3926325 | pmc = 2851632 | doi = 10.1016/S0092-8674(85)80099-4 }}</ref> Subsequently, a different, heterotrimeric plus-end-directed MT-based motor named kinesin-2, consisting of two distinct KHC-related motor subunits and an accessory "KAP" subunit, was purified from echinoderm egg/embryo extracts<ref name="pmid8232586">{{cite journal | vauthors = Cole DG, Chinn SW, Wedaman KP, Hall K, Vuong T, Scholey JM | title = Novel heterotrimeric kinesin-related protein purified from sea urchin eggs | journal = Nature | volume = 366 | issue = 6452 | pages = 268–70 | date = November 1993 | pmid = 8232586 | doi = 10.1038/366268a0 | bibcode = 1993Natur.366..268C | s2cid = 4367715 }}</ref> and is best known for its role in transporting protein complexes ([[intraflagellar transport]] particles) along [[axoneme]]s during [[ciliogenesis]].<ref name="pmid12415299">{{cite journal | vauthors = Rosenbaum JL, Witman GB | title = Intraflagellar transport | journal = Nature Reviews. Molecular Cell Biology | volume = 3 | issue = 11 | pages = 813–25 | date = November 2002 | pmid = 12415299 | doi = 10.1038/nrm952 | s2cid = 12130216 }}</ref> Molecular genetic and genomic approaches have led to the recognition that the kinesins form a diverse superfamily of motors that are responsible for multiple intracellular motility events in eukaryotic cells.<ref name="pmid2522352">{{cite journal | vauthors = Yang JT, Laymon RA, Goldstein LS | title = A three-domain structure of kinesin heavy chain revealed by DNA sequence and microtubule binding analyses | journal = Cell | volume = 56 | issue = 5 | pages = 879–89 | date = March 1989 | pmid = 2522352 | doi = 10.1016/0092-8674(89)90692-2 | s2cid = 44318695 }}</ref><ref name="pmid1447303">{{cite journal | vauthors = Aizawa H, Sekine Y, Takemura R, Zhang Z, Nangaku M, Hirokawa N | title = Kinesin family in murine central nervous system | journal = The Journal of Cell Biology | volume = 119 | issue = 5 | pages = 1287–96 | date = December 1992 | pmid = 1447303 | pmc = 2289715 | doi = 10.1083/jcb.119.5.1287 }}</ref><ref name="pmid2138511">{{cite journal | vauthors = Enos AP, Morris NR | title = Mutation of a gene that encodes a kinesin-like protein blocks nuclear division in A. nidulans | journal = Cell | volume = 60 | issue = 6 | pages = 1019–27 | date = March 1990 | pmid = 2138511 | doi = 10.1016/0092-8674(90)90350-N | s2cid = 27420513 }}</ref><ref name="pmid2138512">{{cite journal | vauthors = Meluh PB, Rose MD | title = KAR3, a kinesin-related gene required for yeast nuclear fusion | journal = Cell | volume = 60 | issue = 6 | pages = 1029–41 | date = March 1990 | pmid = 2138512 | doi = 10.1016/0092-8674(90)90351-E | s2cid = 19660190 }}</ref> For example, the genomes of mammals encode more than 40 kinesin proteins,<ref name="pmid19773780">{{cite journal | vauthors = Hirokawa N, Noda Y, Tanaka Y, Niwa S | title = Kinesin superfamily motor proteins and intracellular transport | journal = Nature Reviews. Molecular Cell Biology | volume = 10 | issue = 10 | pages = 682–96 | date = October 2009 | pmid = 19773780 | doi = 10.1038/nrm2774 | s2cid = 18129292 }}</ref> organized into at least 14 families named kinesin-1 through kinesin-14.<ref name="pmid15479732">{{cite journal | vauthors = Lawrence CJ, Dawe RK, Christie KR, Cleveland DW, Dawson SC, Endow SA, Goldstein LS, Goodson HV, Hirokawa N, Howard J, Malmberg RL, McIntosh JR, Miki H, Mitchison TJ, Okada Y, Reddy AS, Saxton WM, Schliwa M, Scholey JM, Vale RD, Walczak CE, Wordeman L | title = A standardized kinesin nomenclature | journal = The Journal of Cell Biology | volume = 167 | issue = 1 | pages = 19–22 | date = October 2004 | pmid = 15479732 | pmc = 2041940 | doi = 10.1083/jcb.200408113 }}</ref>

== Structure ==

=== Overall structure ===
Members of the kinesin superfamily vary in shape but the prototypical kinesin-1 motor consists of two Kinesin Heavy Chain (KHC) molecules which form a [[protein dimer]] (molecule pair) that binds two light chains (KLCs), which are unique for different cargos.{{cn|date=May 2025}}

The heavy chain of kinesin-1 comprises a globular head (the motor domain) at the amino terminal end connected via a short, flexible neck linker to the stalk – a long, central alpha-helical [[coiled coil]] domain – that ends in a carboxy terminal tail domain which associates with the light-chains. The stalks of two KHCs intertwine to form a [[coiled coil]] that directs dimerization of the two KHCs. In most cases transported cargo binds to the kinesin light chains, at the [[Tetratricopeptide|TPR motif]] sequence of the KLC, but in some cases cargo binds to the C-terminal domains of the heavy chains.<ref name="pmid2522351">{{cite journal | vauthors = Hirokawa N, Pfister KK, Yorifuji H, Wagner MC, Brady ST, Bloom GS | title = Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration | journal = Cell | volume = 56 | issue = 5 | pages = 867–78 | date = March 1989 | pmid = 2522351 | doi = 10.1016/0092-8674(89)90691-0 | s2cid = 731898 }}</ref>

=== Kinesin motor domain ===
{{Infobox protein family
| Symbol = Kinesin motor domain
| Name = Kinesin motor domain
| image = Kinesin_motor_domain_1BG2.png
| width =
| caption = Crystallographic structure of the human kinesin motor domain depicted as a rainbow colored cartoon ([[N-terminus]] = blue, [[C-terminus]] = red) complexed with [[Adenosine diphosphate|ADP]] (stick diagram, carbon = white, oxygen = red, nitrogen = blue, phosphorus = orange) and a [[magnesium]] ion (grey sphere).<ref name="pmid8606779">{{PDB|1BG2}}; {{cite journal | vauthors = Kull FJ, Sablin EP, Lau R, Fletterick RJ, Vale RD | title = Crystal structure of the kinesin motor domain reveals a structural similarity to myosin | journal = Nature | volume = 380 | issue = 6574 | pages = 550–5 | date = April 1996 | pmid = 8606779 | pmc = 2851642 | doi = 10.1038/380550a0 | bibcode = 1996Natur.380..550J }}</ref>
| Pfam= PF00225
| InterPro= IPR001752
| SMART=SM00129
| PROSITE = PS50067
| SCOP = 1bg2
| TCDB =
| OPM family=
| OPM protein=
| CDD= cd00106
}}
The head is the signature of kinesin and its amino acid sequence is well conserved among various kinesins. Each head has two separate [[binding site]]s: one for the microtubule and the other for ATP.  ATP binding and hydrolysis as well as [[Adenosine diphosphate|ADP]] release change the conformation of the microtubule-binding domains and the orientation of the neck linker with respect to the head; this results in the motion of the kinesin.  Several structural elements in the head, including a central [[beta-sheet]] domain and the Switch I and II domains, have been implicated as mediating the interactions between the two binding sites and the neck domain.  Kinesins are structurally related to [[G proteins]], which hydrolyze [[Guanosine triphosphate|GTP]] instead of ATP. Several structural elements are shared between the two families, notably the Switch I and Switch II domain.
[[File:OpenClose.gif|thumb|Mobile and self-inhibited conformations of kinesin-1. '''Self-inhibited conformation:'''IAK region of the tail (green) binds to motor domains (yellow and orange) to inhibit the enzymatic cycle of kinesin-1.'''Mobile conformation:''' Absent the tail binding, kinesin-1 motor domains (yellow and orange) can move freely along the [[microtubule]](MT).<ref name=":3">{{cite journal | vauthors = Kaan HY, Hackney DD, Kozielski F | title = The structure of the kinesin-1 motor-tail complex reveals the mechanism of autoinhibition | journal = Science | volume = 333 | issue = 6044 | pages = 883–5 | date = August 2011 | pmid = 21836017 | pmc = 3339660 | doi = 10.1126/science.1204824 | bibcode = 2011Sci...333..883K }}</ref> PDB 2Y65; PDB 2Y5W.]]
[[File:Re Zoom.gif|thumb|Detailed view of kinesin-1 self-inhibition (one of two possible conformations shown). Highlight: positively charged residues (blue) of the IAK region interact at multiple locations with negatively charged residues (red) of the motor domains<ref name=":3" /> PDB 2Y65]]

=== Basic kinesin regulation ===
Kinesins tend to have low basal enzymatic activity which becomes significant when microtubule-activated.<ref name="pmid8506368">{{cite journal | vauthors = Stewart RJ, Thaler JP, Goldstein LS | title = Direction of microtubule movement is an intrinsic property of the motor domains of kinesin heavy chain and Drosophila ncd protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 11 | pages = 5209–13 | date = June 1993 | pmid = 8506368 | doi = 10.1073/pnas.90.11.5209 | pmc = 46685 | bibcode = 1993PNAS...90.5209S | doi-access = free }}</ref> In addition, many members of the kinesin superfamily can be self-inhibited by the binding of tail domain to the motor domain.<ref name="pmid19851335">{{cite journal | vauthors = Verhey KJ, Hammond JW | title = Traffic control: regulation of kinesin motors | journal = Nature Reviews. Molecular Cell Biology | volume = 10 | issue = 11 | pages = 765–77 | date = November 2009 | pmid = 19851335 | doi = 10.1038/nrm2782 | s2cid = 10713993 }}</ref> Such self-inhibition can then be relieved via additional regulation such as binding to cargo, cargo adapters or other [[microtubule-associated proteins]].<ref>{{cite journal | vauthors = Siddiqui N, Zwetsloot AJ, Bachmann A, Roth D, Hussain H, Brandt J, Kaverina I, Straube A | display-authors = 6 | title = PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport | journal = Nature Communications | volume = 10 | issue = 1 | article-number = 2693 | date = June 2019 | pmid = 31217419 | pmc = 6584639 | doi = 10.1038/s41467-019-10644-9 | bibcode = 2019NatCo..10.2693S }}</ref><ref>{{cite journal | vauthors = Blasius TL, Cai D, Jih GT, Toret CP, Verhey KJ | title = Two binding partners cooperate to activate the molecular motor Kinesin-1 | journal = The Journal of Cell Biology | volume = 176 | issue = 1 | pages = 11–7 | date = January 2007 | pmid = 17200414 | pmc = 2063617 | doi = 10.1083/jcb.200605099 }}</ref><ref>{{cite journal | vauthors = Hooikaas PJ, Martin M, Mühlethaler T, Kuijntjes GJ, Peeters CA, Katrukha EA, Ferrari L, Stucchi R, Verhagen DG, van Riel WE, Grigoriev I, Altelaar AF, Hoogenraad CC, Rüdiger SG, Steinmetz MO, Kapitein LC, Akhmanova A | display-authors = 6 | title = MAP7 family proteins regulate kinesin-1 recruitment and activation | journal = The Journal of Cell Biology | volume = 218 | issue = 4 | pages = 1298–1318 | date = April 2019 | pmid = 30770434 | doi = 10.1083/jcb.201808065 | pmc = 6446838 }}</ref>

== Cargo transport ==
In the cell, small molecules, such as gases and [[glucose]], [[Brownian motion|diffuse]] to where they are needed.{{cn|date=August 2025}} Large molecules synthesised in the cell body, intracellular components such as [[vesicle (biology)|vesicle]]s and organelles such as [[mitochondria]] are too large (and the [[cytosol]] too crowded) to be able to diffuse to their destinations.  Motor proteins fulfill the role of transporting large cargo about the cell to their required destinations. Kinesins are motor proteins that transport such cargo by walking unidirectionally along [[microtubule]] tracks hydrolysing one molecule of [[adenosine triphosphate]] (ATP) at each step.<ref name="Schnitzer">{{cite journal | vauthors = Schnitzer MJ, Block SM | title = Kinesin hydrolyses one ATP per 8-nm step | journal = Nature | volume = 388 | issue = 6640 | pages = 386–90 | date = July 1997 | pmid = 9237757 | doi = 10.1038/41111 | bibcode = 1997Natur.388..386S | s2cid = 4363000 | doi-access = free }}</ref> It was thought that ATP [[hydrolysis]] powered each step, the energy released propelling the head forwards to the next binding site.<ref name="pmid10753125">{{cite journal | vauthors = Vale RD, Milligan RA | title = The way things move: looking under the hood of molecular motor proteins | journal = Science | volume = 288 | issue = 5463 | pages = 88–95 | date = April 2000 | pmid = 10753125 | doi = 10.1126/science.288.5463.88 | bibcode = 2000Sci...288...88V }}</ref> However, it has been proposed that the head diffuses forward and the force of binding to the microtubule is what pulls the cargo along.<ref name="Mather">{{cite journal | vauthors = Mather WH, Fox RF | title = Kinesin's biased stepping mechanism: amplification of neck linker zippering | journal = Biophysical Journal | volume = 91 | issue = 7 | pages = 2416–26 | date = October 2006 | pmid = 16844749 | pmc = 1562392 | doi = 10.1529/biophysj.106.087049 | bibcode = 2006BpJ....91.2416M }}</ref> In addition viruses, HIV for example, exploit kinesins to allow virus particle shuttling after assembly.<ref>{{cite journal | vauthors = Gaudin R, de Alencar BC, Jouve M, Bèrre S, Le Bouder E, Schindler M, Varthaman A, Gobert FX, Benaroch P | title = Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages | journal = The Journal of Cell Biology | volume = 199 | issue = 3 | pages = 467–79 | date = October 2012 | pmid = 23091068 | pmc = 3483138 | doi = 10.1083/jcb.201201144 }}</ref>

There is significant evidence that cargoes in-vivo are transported by multiple motors.<ref name="pmid17580082">{{cite journal | vauthors = Gross SP, Vershinin M, Shubeita GT | title = Cargo transport: two motors are sometimes better than one | journal = Current Biology | volume = 17 | issue = 12 | pages = R478–86 | date = June 2007 | pmid = 17580082 | doi = 10.1016/j.cub.2007.04.025 | s2cid = 8791125 | doi-access = free | bibcode = 2007CBio...17.R478G }}</ref><ref name="pmid18727910">{{cite journal | vauthors = Hancock WO | title = Intracellular transport: kinesins working together | journal = Current Biology | volume = 18 | issue = 16 | pages = R715–7 | date = August 2008 | pmid = 18727910 | doi = 10.1016/j.cub.2008.07.068 | s2cid = 7540556 | doi-access = free | bibcode = 2008CBio...18.R715H }}</ref><ref name="pmid18701289">{{cite journal | vauthors = Kunwar A, Vershinin M, Xu J, Gross SP | title = Stepping, strain gating, and an unexpected force-velocity curve for multiple-motor-based transport | journal = Current Biology | volume = 18 | issue = 16 | pages = 1173–83 | date = August 2008 | pmid = 18701289 | pmc = 3385514 | doi = 10.1016/j.cub.2008.07.027 | bibcode = 2008CBio...18.1173K }}</ref><ref name="pmid16287974">{{cite journal | vauthors = Klumpp S, Lipowsky R | title = Cooperative cargo transport by several molecular motors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 48 | pages = 17284–9 | date = November 2005 | pmid = 16287974 | pmc = 1283533 | doi = 10.1073/pnas.0507363102 | arxiv = q-bio/0512011 | bibcode = 2005PNAS..10217284K | doi-access = free }}</ref>

== Direction of motion ==
Motor proteins travel in a specific direction along a microtubule. Microtubules are polar; meaning, the heads only bind to the microtubule in one orientation, while ATP binding gives each step its direction through a process known as neck linker zippering.<ref>{{cite journal | vauthors = Rice S, Lin AW, Safer D, Hart CL, Naber N, Carragher BO, Cain SM, Pechatnikova E, Wilson-Kubalek EM, Whittaker M, Pate E, Cooke R, Taylor EW, Milligan RA, Vale RD | title = A structural change in the kinesin motor protein that drives motility | journal = Nature | volume = 402 | issue = 6763 | pages = 778–84 | date = December 1999 | pmid = 10617199 | doi = 10.1038/45483 | bibcode = 1999Natur.402..778R | s2cid = 573909 }}</ref>

It has been previously known that kinesin move cargo towards the plus (+) end of a microtubule, also known as anterograde transport/orthograde transport.<ref name=":2">{{Cite journal |last1=Lodish |first1=Harvey |last2=Berk |first2=Arnold |last3=Zipursky |first3=S. Lawrence |last4=Matsudaira |first4=Paul |last5=Baltimore |first5=David |last6=Darnell |first6=James | name-list-style = vanc |date=2000 |title=Kinesin, Dynein, and Intracellular Transport |url= https://www.ncbi.nlm.nih.gov/books/NBK21710/ |archive-url= https://web.archive.org/web/20201111171040/https://www.ncbi.nlm.nih.gov/books/NBK21710/ |archive-date= 11 November 2020 }}</ref> However, it has been recently discovered that in budding yeast cells kinesin Cin8 (a member of the Kinesin-5 family) can move toward the minus end as well, or retrograde transport.  This means, these unique yeast kinesin homotetramers have the novel ability to move bi-directionally.<ref>{{cite journal | vauthors = Roostalu J, Hentrich C, Bieling P, Telley IA, Schiebel E, Surrey T | title = Directional switching of the kinesin Cin8 through motor coupling | journal = Science | volume = 332 | issue = 6025 | pages = 94–9 | date = April 2011 | pmid = 21350123 | doi = 10.1126/science.1199945 | s2cid = 90739364 | bibcode = 2011Sci...332...94R }}</ref><ref>{{cite journal | vauthors = Fallesen T, Roostalu J, Duellberg C, Pruessner G, Surrey T | title = Ensembles of Bidirectional Kinesin Cin8 Produce Additive Forces in Both Directions of Movement | journal = Biophysical Journal | volume = 113 | issue = 9 | pages = 2055–2067 | date = November 2017 | pmid = 29117528 | pmc = 5685778 | doi = 10.1016/j.bpj.2017.09.006 | bibcode = 2017BpJ...113.2055F }}</ref><ref>{{cite journal | vauthors = Edamatsu M | title = Bidirectional motility of the fission yeast kinesin-5, Cut7 | journal = Biochemical and Biophysical Research Communications | volume = 446 | issue = 1 | pages = 231–4 | date = March 2014 | pmid = 24589736 | doi = 10.1016/j.bbrc.2014.02.106 }}</ref> Kinesin, so far, has only been shown to move toward the minus end when in a group, with motors sliding in the antiparallel direction in an attempt to separate microtubules.<ref name=":02">{{cite journal | vauthors = Roostalu J, Hentrich C, Bieling P, Telley IA, Schiebel E, Surrey T | title = Directional switching of the kinesin Cin8 through motor coupling | journal = Science | volume = 332 | issue = 6025 | pages = 94–9 | date = April 2011 | pmid = 21350123 | doi = 10.1126/science.1199945 | s2cid = 90739364 | bibcode = 2011Sci...332...94R }}</ref> This dual directionality has been observed in identical conditions where free Cin8 molecules move towards the minus end, but cross-linking Cin8 move toward the plus ends of each cross-linked microtubule. One specific study tested the speed at which Cin8 motors moved, their results yielded a range of about 25-55&nbsp;nm/s, in the direction of the spindle poles.<ref name=":1">{{cite journal | vauthors = Gerson-Gurwitz A, Thiede C, Movshovich N, Fridman V, Podolskaya M, Danieli T, Lakämper S, Klopfenstein DR, Schmidt CF, Gheber L | display-authors = 6 | title = Directionality of individual kinesin-5 Cin8 motors is modulated by loop 8, ionic strength and microtubule geometry | journal = The EMBO Journal | volume = 30 | issue = 24 | pages = 4942–54 | date = November 2011 | pmid = 22101328 | pmc = 3243633 | doi = 10.1038/emboj.2011.403 }}</ref> On an individual basis it has been found that by varying ionic conditions Cin8 motors can become as fast as 380&nbsp;nm/s.<ref name=":1" />  It is suggested that the bidirectionality of yeast kinesin-5 motors such as Cin8 and Cut7 is a result of coupling with other Cin8 motors and helps to fulfill the role of dynein in budding yeast, as opposed to the human homologue of these motors, the plus directed Eg5.<ref>{{cite journal | vauthors = Valentine MT, Fordyce PM, Block SM | title = Eg5 steps it up! | journal = Cell Division | volume = 1 | issue = 1 | article-number = 31 | date = December 2006 | pmid = 17173688 | pmc = 1716758 | doi = 10.1186/1747-1028-1-31 | url =  | doi-access = free }}</ref> This discovery in kinesin-14 family proteins (such as&nbsp;''[[Drosophila melanogaster]]'' NCD, budding yeast KAR3, and&nbsp;''[[Arabidopsis thaliana]]''&nbsp;ATK5) allows kinesin to walk in the opposite direction, toward microtubule minus end.<ref>{{cite journal | vauthors = Ambrose JC, Li W, Marcus A, Ma H, Cyr R | title = A minus-end-directed kinesin with plus-end tracking protein activity is involved in spindle morphogenesis | journal = Molecular Biology of the Cell | volume = 16 | issue = 4 | pages = 1584–92 | date = April 2005 | pmid = 15659646 | pmc = 1073643 | doi = 10.1091/mbc.e04-10-0935 }}</ref> This is not typical of kinesin, rather, an exception to the normal direction of movement.

[[Image:Motility of kinesin en.png|thumb|Diagram illustrating motility of kinesin.]]Another type of motor protein, known as&nbsp;[[dynein]]s, move towards the minus end of the microtubule. Thus, they transport cargo from the periphery of the cell towards the center. An example of this would be transport occurring from the terminal boutons of a neuronal axon to the cell body (soma). This is known as&nbsp;''retrograde transport''.

== Mechanism of movement ==
In 2023 direct visualization of kinesin  "walking" along a microtubule in real-time was reported.<ref name="Fei">{{cite journal |last1=Fei |first1=Jinyu |last2=Zhou |first2=Ruobu |title=Watching biomolecules stride in real time |journal=Science |date=10 March 2023 |volume=379 |issue=6636 |pages=986–987 |doi=10.1126/science.adg8451|pmid=36893224 |pmc=10318587 |bibcode=2023Sci...379..986F }}</ref> In a "hand-over-hand" mechanism, the kinesin heads step past one another, alternating the lead position. Thus in each step the leading head becomes the trailing head, while the trailing head becomes the leading head.

* This cycle begins with the trailing head releasing inorganic phosphate (Pi) derived from the hydrolysis of ATP.
* The trailing head detaches from the microtubule and rotates into its rightward displaced unbound state.
* The leading head binds ATP which causes the neck linker to dock to it, which moves the trailing head around the leading head into a position further along the microtubule in the direction of travel. The trailing head remains unbound.
* The ATP in the leading head is hydrolyzed.
* The trailing head releases its ADP and the binds to the microtubule becoming the leading head.<ref name="Deguchi">{{cite journal |last1=Deguchi |first1=Takahiro |title=Direct observation of motor protein stepping in living cells using MINFLUX |journal=Science |date=10 March 2023 |volume=379 |issue=6636 |pages=1010–1015 |doi=10.1126/science.ade2676|pmid=36893247 |pmc=7614483 |bibcode=2023Sci...379.1010D }}</ref><ref name="Wolff">{{cite journal |last1=Wolff |first1=Jan |last2=Scheiderer |first2=Lukas |last3=Engelhardt |first3=Tobias |last4=Engelhardt |first4=Johann |last5=Matthias |first5=Jessica |last6=Hell |first6=Stefan |title=MINFLUX dissects the unimpeded walking of kinesin-1 |journal=Science |date=10 March 2023 |volume=379 |issue=6636 |pages=1004–1010 |doi=10.1126/science.ade2650|pmid=36893244 |bibcode=2023Sci...379.1004W |s2cid=251162014 }}</ref><ref name="Yildiz et al.">{{cite journal | vauthors = Yildiz A, Tomishige M, Vale RD, Selvin PR |author4-link=Paul R. Selvin |author1-link=Ahmet Yıldız (scientist) | title = Kinesin walks hand-over-hand | journal = Science | volume = 303 | issue = 5658 | pages = 676–8 | date = January 2004 | pmid = 14684828 | doi = 10.1126/science.1093753 | bibcode = 2004Sci...303..676Y | s2cid = 30529199 }}</ref><ref name="Asbury">{{cite journal | vauthors = Asbury CL | title = Kinesin: world's tiniest biped | journal = Current Opinion in Cell Biology | volume = 17 | issue = 1 | pages = 89–97 | date = February 2005 | pmid = 15661524 | doi = 10.1016/j.ceb.2004.12.002 }}</ref><ref name="pmid20160108">{{cite journal | vauthors = Sindelar CV, Downing KH | title = An atomic-level mechanism for activation of the kinesin molecular motors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 9 | pages = 4111–6 | date = March 2010 | pmid = 20160108 | pmc = 2840164 | doi = 10.1073/pnas.0911208107 | bibcode = 2010PNAS..107.4111S | doi-access = free }}</ref><ref>{{cite web|url= http://phys.org/news185699532.html|title=Life's smallest motor, cargo carrier of the cells, moves like a seesaw|author=Lay Summary|publisher=PhysOrg.com|date=18 February 2010|access-date=31 May 2013}}</ref>

== Theoretical modeling ==
A number of theoretical models of the molecular motor protein kinesin have been proposed.<ref name="Atzberger">{{cite journal | vauthors = Atzberger PJ, Peskin CS | title = A Brownian Dynamics model of kinesin in three dimensions incorporating the force-extension profile of the coiled-coil cargo tether | journal = Bulletin of Mathematical Biology | volume = 68 | issue = 1 | pages = 131–60 | date = January 2006 | pmid = 16794924 | doi = 10.1007/s11538-005-9003-6 | arxiv = 0910.5753 | s2cid = 13534734 }}</ref><ref name="Oster">{{cite journal | vauthors = Peskin CS, Oster G | title = Coordinated hydrolysis explains the mechanical behavior of kinesin | journal = Biophysical Journal | volume = 68 | issue = 4 Suppl | pages = 202S–210S; discussion 210S–211S | date = April 1995 | pmid = 7787069 | pmc = 1281917 }}</ref><ref name="Mogilner">{{cite journal | vauthors = Mogilner A, Fisher AJ, Baskin RJ | title = Structural changes in the neck linker of kinesin explain the load dependence of the motor's mechanical cycle | journal = Journal of Theoretical Biology | volume = 211 | issue = 2 | pages = 143–57 | date = July 2001 | pmid = 11419956 | doi = 10.1006/jtbi.2001.2336 | bibcode = 2001JThBi.211..143M }}</ref> Many challenges are encountered in theoretical investigations given the remaining uncertainties about the roles of protein structures, the precise way energy from ATP is transformed into mechanical work, and the roles played by thermal fluctuations.  This is a rather active area of research.  There is a need especially for approaches which better make a link with the molecular architecture of the protein and data obtained from experimental investigations.

The single-molecule dynamics are already well described<ref name=":0">{{cite journal| vauthors = Celis-Garza D, Teimouri H, Kolomeisky AB  |title=Correlations and symmetry of interactions influence collective dynamics of molecular motors |journal=Journal of Statistical Mechanics: Theory and Experiment |volume=2015 |issue=4 |doi=10.1088/1742-5468/2015/04/p04013|article-number=P04013|year=2015|arxiv=1503.00633 |bibcode=2015JSMTE..04..013C|s2cid=14002728}}</ref> but it seems that these nano scale machines typically work in large teams.

Single-molecule dynamics are based on the distinct chemical states of the motor and observations about its mechanical steps.<ref name=":4">{{Cite journal|last1=Liepelt|first1=Steffen|last2=Lipowsky|first2=Reinhard|date=2007-06-20|title=Kinesin's Network of Chemomechanical Motor Cycles|url=https://link.aps.org/doi/10.1103/PhysRevLett.98.258102|journal=Physical Review Letters|volume=98|issue=25|article-number=258102|doi=10.1103/PhysRevLett.98.258102|pmid=17678059|bibcode=2007PhRvL..98y8102L|url-access=subscription}}</ref> For small concentrations of adenosine diphosphate, the motor's behaviour is governed by the competition of two chemomechanical motor cycles which determine the motor's stall force. A third cycle becomes important for large ADP concentrations.<ref name=":4" /> Models with a single cycle have been discussed too. Seiferth et al. demonstrated how quantities such as the velocity or the [[entropy production]] of a motor change when adjacent states are merged in a multi-cyclic model until eventually the number of cycles is reduced.<ref>{{Cite journal|last1=Seiferth|first1=David|last2=Sollich|first2=Peter|last3=Klumpp|first3=Stefan|date=2020-12-29|title=Coarse graining of biochemical systems described by discrete stochastic dynamics|url=https://link.aps.org/doi/10.1103/PhysRevE.102.062149|journal=Physical Review E|volume=102|issue=6|article-number=062149|doi=10.1103/PhysRevE.102.062149|pmid=33466014|arxiv=2102.13394|bibcode=2020PhRvE.102f2149S|s2cid=231652939}}</ref>

Recent experimental research has shown that kinesins, while moving along microtubules, interact with each other,<ref>{{cite journal|vauthors=Seitz A, Surrey T|date=January 2006|title=Processive movement of single kinesins on crowded microtubules visualized using quantum dots|journal=The EMBO Journal|volume=25|issue=2|pages=267–77|doi=10.1038/sj.emboj.7600937|pmc=1383520|pmid=16407972}}</ref><ref>{{cite journal|vauthors=Vilfan A, Frey E, Schwabl F, Thormählen M, Song YH, Mandelkow E|date=October 2001|title=Dynamics and cooperativity of microtubule decoration by the motor protein kinesin|journal=Journal of Molecular Biology|volume=312|issue=5|pages=1011–26|doi=10.1006/jmbi.2001.5020|pmid=11580246}}</ref>  the interactions being short range and weak attractive (1.6±0.5 K<sub>B</sub>T).  One model that has been developed takes into account these particle interactions,<ref name=":0" /> where the dynamic rates change accordingly with the energy of interaction. If the energy is positive the rate of creating bonds (q) will be higher while the rate of breaking bonds (r) will be lower. One can understand that the rates of entrance and exit in the microtubule will be changed as well by the energy (See figure 1 in reference 30). If the second site is occupied the rate of entrance will be α*q and if the last but one site is occupied the rate of exit will be β*r. This theoretical approach agrees with the results of Monte Carlo simulations for this model, especially for the limiting case of very large negative energy. The normal totally asymmetric simple exclusion process for (or TASEP) results can be recovered from this model making the energy equal to zero.

:<math display="display">{q\over r} = e^{E\over K_B T}</math>

== Mitosis ==
In recent years, it has been found that microtubule-based molecular motors (including a number of kinesins) have a role in [[mitosis]] (cell division). Kinesins are important for proper spindle length and are involved in sliding microtubules apart within the spindle during prometaphase and metaphase, as well as depolymerizing microtubule minus ends at centrosomes during anaphase.<ref name="Goshima">{{cite journal | vauthors = Goshima G, Vale RD | title = Cell cycle-dependent dynamics and regulation of mitotic kinesins in Drosophila S2 cells | journal = Molecular Biology of the Cell | volume = 16 | issue = 8 | pages = 3896–907 | date = August 2005 | pmid = 15958489 | pmc = 1182325 | doi = 10.1091/mbc.E05-02-0118 }}</ref> Specifically, Kinesin-5 family proteins act within the spindle to slide microtubules apart, while the [[Kinesin 13]] family act to depolymerize microtubules.

== Kinesin superfamily ==
Human kinesin superfamily members include the following proteins, which in the standardized nomenclature developed by the community of kinesin researchers, are organized into 14 families named kinesin-1 through kinesin-14:<ref name="pmid15479732"/>
* 1A – [[KIF1A]], 1B – [[KIF1B]], 1C – [[KIF1C]]  = kinesin-3
* 2A – [[KIF2A]], 2C – [[KIF2C]] = kinesin-13
* 3B – [[KIF3B]] or 3C – [[KIF3C]] ，3A - [[KIF3A]] = kinesin-2
* 4A – [[KIF4A]], 4B – [[KIF4B]] = kinesin-4
* 5A – [[KIF5A]], 5B – [[KIF5B]], 5C – [[KIF5C]] = kinesin-1
* 6 – [[KIF6]] = kinesin-9 
* 7 – [[KIF7]] = kinesin-4
* 9 – [[KIF9]] = kinesin-9
* 11 – [[KIF11]] = kinesin-5
* 12 – [[KIF12]] = kinesin-12
* 13A – [[KIF13A]], 13B – [[KIF13B]] = kinesin-3
* 14 – [[KIF14]] = kinesin-3
* 15 – [[KIF15]] = kinesin-12
* 16B – [[KIF16B]] = kinesin-3
* 17 – [[KIF17]] = kinesin-2
* 18A – [[KIF18A]], 18B – [[KIF18B]] = kinesin-8
* 19 – [[KIF19]] = kinesin-8
* 20A – [[KIF20A]], 20B – [[KIF20B]] = kinesin-6
* 21A – [[KIF21A]], 21B – [[KIF21B]] = kinesin-4
* 22 – [[KIF22]] = kinesin-10
* 23 – [[KIF23]] = kinesin-6
* 24 – [[KIF24]] = kinesin-13
* 25 – [[KIF25]] = kinesin-14
* 26A – [[KIF26A]], 26B – [[KIF26B]] = kinesin-11
* 27 – [[KIF27]] = kinesin-4
* C1 – [[KIFC1]], C2 – [[KIFC2]], C3 – [[KIFC3]] = kinesin-14

kinesin-1 light chains:
* 1 – [[KLC1]], 2 – [[KLC2]], 3 – [[KLC3]], 4 – [[KLC4]]

kinesin-2 associated protein:
* [[KIFAP3]] (also known as KAP-1, KAP3)

== See also ==
{{Portal|Biology}}
*[[Axonal transport]]
*[[Dynein]]
*[[Intraflagellar transport]] along [[cilia]]
*[[Kinesin 8]]
*[[Kinesin 13]]
*[[KRP (biochemistry)|KRP]]
*[[Molecular motor]]
*[[Transport by multiple-motor proteins]]

== References ==
{{Reflist|2}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Lawrence CJ, Dawe RK, Christie KR, Cleveland DW, Dawson SC, Endow SA, Goldstein LS, Goodson HV, Hirokawa N, Howard J, Malmberg RL, McIntosh JR, Miki H, Mitchison TJ, Okada Y, Reddy AS, Saxton WM, Schliwa M, Scholey JM, Vale RD, Walczak CE, Wordeman L | title = A standardized kinesin nomenclature | journal = The Journal of Cell Biology | volume = 167 | issue = 1 | pages = 19–22 | date = October 2004 | pmid = 15479732 | pmc = 2041940 | doi = 10.1083/jcb.200408113 }}
{{refend}}

== External links ==
*{{usurped|1=[https://archive.today/20140227171446/http://www.mechanobio.info/modules/go-0030705#3_go-0030705 MBInfo - Kinesin transports cargo along microtubules]}}
*[http://valelab.ucsf.edu/ Animated model of kinesin walking] {{Webarchive|url=https://web.archive.org/web/20240315062956/https://valelab.ucsf.edu/ |date=15 March 2024 }}
*[https://www.ibiology.org/cell-biology/motor-proteins/ Ron Vale's Seminar: "Molecular Motor Proteins"]
*[https://web.archive.org/web/20090922112210/http://cellimages.ascb.org/cdm4/item_viewer.php?CISOROOT=%2Fp4041coll12&CISOPTR=53&CISOBOX=1&REC=1 Animation of kinesin movement] ASCB image library
* {{cite web |url=http://tissue.medicalengineer.co.uk/Cellular+Motility+in+Brief.php |title=Microtubule Based Movement |last=Murphy |first=V.F. |work=tissue.medicalengineer.co.uk |date=2004-05-12 |archive-url=https://web.archive.org/web/20070722103457/http://tissue.medicalengineer.co.uk/Cellular%2BMotility%2Bin%2BBrief.php |archive-date=2007-07-22 |access-date=2015-12-10 }}
*[http://www.studiodaily.com/main/technique/tprojects/6850.html The Inner Life of a Cell, 3D animation featuring a Kinesin transporting a vesicle] {{Webarchive|url=https://web.archive.org/web/20081207201909/http://www.studiodaily.com/main/technique/tprojects/6850.html |date=7 December 2008 }}
*[https://web.archive.org/web/20150906060933/http://labs.cellbio.duke.edu/kinesin/ The Kinesin Homepage]
*{{MeshName|Kinesin}}
*{{EC number|3.6.4.4}}
*{{EC number|3.6.4.5}}
* [http://www.pdbe.org/emsearch/kinesin 3D electron microscopy structures of kinesin from the EM Data Bank(EMDB)]

{{Cytoskeletal Proteins}}
{{ATPases}}
{{Authority control}}

[[Category:Motor proteins]]