View source for COPI

{{Short description|Protein complex}}
{{other uses}}
{{redirect|COP 1|the climate change conference|United Nations Climate Change conference#1995: COP 1, Berlin, Germany{{!}}1995 United Nations Climate Change conference}}
[[File:COPI_coated_vesicles.png|thumb|263x263px|Electron micrograph of in vitro–formed COPI-coated vesicles. Average vesicle diameter at the membrane level is 60 nm.]]
{{use dmy dates|date=October 2025}}
'''COPI''' is a [[coatomer]], a protein complex<ref>{{MeshName|Coat+Protein+Complex+I}}</ref> that coats [[vesicle (biology)|vesicle]]s transporting proteins from the ''cis'' end of the [[Golgi complex]] back to the rough [[endoplasmic reticulum]] (ER), where they were originally [[Translation (genetics)|synthesized]], and between Golgi compartments.  This type of transport{{Clarify|reason=does this include the transport between the Golgi compartments|date=February 2021}} is ''retrograde transport'', in contrast to the ''anterograde transport'' associated with the [[COPII]] protein.  The name "COPI" refers to the specific coat protein complex that initiates the budding process on the ''cis''-Golgi membrane.  The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, [[Archain|δ]], ε and [[COPZ1|ζ]].

{{Infobox protein family
| Symbol = COPI_C
| Name = COPI
| image =
| width =
| caption =
| Pfam = PF06957
| Pfam_clan =
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
| InterPro = IPR010714
}}

==Coat proteins==
Coat protein, or COPI, is an [[ADP ribosylation factor]] (ARF)-dependent protein involved in membrane traffic.<ref name="pmid1680566">{{cite journal| doi=10.1016/0092-8674(91)90176-Y| vauthors=Serafini T, Orci L, Amherdt M, Brunner M, Kahn RA, Rothman JE| title=ADP-ribosylation factor is a subunit of the coat of Golgi-derived COP-coated vesicles: a novel role for a GTP-binding protein. | journal=Cell | year= 1991 | volume= 67 | issue= 2 | pages= 239–53 | pmid=1680566 | s2cid=9766090| doi-access=free }}</ref> COPI was first identified in retrograde traffic from the ''cis''-Golgi to the rough endoplasmic reticulum (ER)<ref>{{cite journal | vauthors = Schekman R, Orci L | year = 1996 | title = Coat proteins and vesicle budding | journal = Science | volume = 271 | issue =5255 | pages = 1526–1533 | doi=10.1126/science.271.5255.1526 | pmid=8599108| bibcode = 1996Sci...271.1526S | s2cid = 30752342 }}</ref><ref name="pmid9261053">{{cite journal| doi=10.1016/S0955-0674(97)80023-3| vauthors=Cosson P, Letourneur F| title=Coatomer (COPI)-coated vesicles: role in intracellular transport and protein sorting. | journal=Curr Opin Cell Biol | year= 1997 | volume= 9 | issue= 4 | pages= 484–7 | pmid=9261053 }}</ref> and is the most extensively studied of ARF-dependent adaptors. COPI consists of seven subunits which compose the heteroheptameric protein complex.

The primary function of adaptors is the selection of cargo proteins for their incorporation into nascent carriers.  Cargo containing the sorting motifs KKXX and KXKXX interact with COPI to form carriers which are transported from the cis-Golgi to the ER.<ref name="pmid8001155">{{cite journal| doi=10.1016/0092-8674(94)90011-6| vauthors=Letourneur F, Gaynor EC, Hennecke S, Démollière C, Duden R, Emr SD| title=Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum. | journal=Cell | year= 1994 | volume= 79 | issue= 7 | pages= 1199–207 | pmid=8001155 | s2cid=9684135|display-authors=etal}}</ref><ref name="pmid8947548">{{cite journal| doi=10.1083/jcb.135.5.1239| vauthors=Sohn K, Orci L, Ravazzola M, Amherdt M, Bremser M, Lottspeich F| title=A major transmembrane protein of Golgi-derived COPI-coated vesicles involved in coatomer binding | journal=J Cell Biol | year= 1996 | volume= 135 | issue= 5 | pages= 1239–48 | pmid=8947548 | pmc=2121093 |display-authors=etal}}</ref><ref name="pmid8830771">{{cite journal| doi=10.1083/jcb.134.6.1411| vauthors=Sönnichsen B, Watson R, Clausen H, Misteli T, Warren G| title=Sorting by COP I-coated vesicles under interphase and mitotic conditions | journal=J Cell Biol | year= 1996 | volume= 134 | issue= 6 | pages= 1411–25 | pmid=8830771 | pmc=2120996 }}</ref><ref name="pmid9244307">{{cite journal| doi=10.1016/S0092-8674(00)80341-4| vauthors=Orci L, Stamnes M, Ravazzola M, Amherdt M, Perrelet A, Söllner TH| title=Bidirectional transport by distinct populations of COPI-coated vesicles | journal=Cell | year= 1997 | volume= 90 | issue= 2 | pages= 335–49 | pmid=9244307 | s2cid=18246842|display-authors=etal| doi-access=free }}</ref><ref name="Ma 926–937">{{Cite journal|last1=Ma|first1=Wenfu|last2=Goldberg|first2=Jonathan|date=2013-04-03|title=Rules for the recognition of dilysine retrieval motifs by coatomer|journal=The EMBO Journal|volume=32|issue=7|pages=926–937|doi=10.1038/emboj.2013.41|issn=1460-2075|pmc=3616288|pmid=23481256}}</ref> Current views suggest that ARFs are also involved in the selection of cargo for incorporation into carriers.

==Budding process==
ADP ribosylation factor (ARF) is a GTPase involved in membrane traffic. There are 6 mammalian ARFs which are regulated by over 30 [[guanine nucleotide exchange factors]] (GEFs) and [[GTPase activating proteins]] (GAPs). ARF is post-translationally modified at the N-terminus by the addition of the fatty acid [[myristic acid |myristate]].

ARF cycles between GTP and GDP-bound conformations. In the GTP-bound form, ARF conformation changes such that the myristate and hydrophobic N-terminal become more exposed and associate with the membrane. The interconversion between GTP and GDP bound states is mediated by ARF [[guanine nucleotide exchange factors|GEFs]] and ARF [[GTPase activating proteins |GAPs]]. At the membrane, ARF-GTP is hydrolyzed to ARF-GDP by ARF GAPs. Once in the GDP-bound conformation, ARF converts to a less hydrophobic conformation and dissociates from the membrane. Soluble ARF-GDP is converted back to ARF-GTP by GEFs.

# Luminal proteins: Proteins found in the lumen of the Golgi complex that need to be transported to the lumen of the ER contain the [[signal peptide]] [[KDEL (amino acid sequence)|KDEL]].<ref name="KDEL and KKXX retrieval">{{cite journal| author=Mariano Stornaiuolo| author2=Lavinia V. Lotti| author3=Nica Borgese| author4=Maria-Rosaria Torrisi| author5=Giovanna Mottola| author6=Gianluca Martire| author7=Stefano Bonatti| name-list-style=amp|date=March 2003| title=KDEL and KKXX Retrieval Signals Appended to the Same Reporter Protein Determine Different Trafficking between Endoplasmic Reticulum, Intermediate Compartment, and Golgi Complex| journal=Molecular Biology of the Cell| volume=14|issue=3| pages=889–902| doi=10.1091/mbc.E02-08-0468| pmid=12631711| pmc=151567}}</ref> This sequence is recognized by a membrane-bound KDEL receptor. In yeast, this is [[ERD2P]] and in mammals it is [[KDELR]]. This receptor then binds to an ARF-GEF, a class of guanine nucleotide exchange factors. This protein in turn binds to the ARF. This interaction causes ARF to exchange its bound [[Guanosine diphosphate|GDP]] for [[Guanosine triphosphate|GTP]]. Once this exchange is made ARF binds to the cytosolic side of the cis-Golgi membrane and inserts the myristoylated N-terminal amphipathic alpha-helix into the membrane.<ref>{{Cite journal|last=Goldberg|first=J.|date=1998-10-16|title=Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching|journal=Cell|volume=95|issue=2|pages=237–248|issn=0092-8674|pmid=9790530|doi=10.1016/s0092-8674(00)81754-7|s2cid=15759753|doi-access=free}}</ref>
# Membrane proteins: Transmembrane proteins which reside in the ER contain sorting signals in their cytosolic tails which direct the protein to exit the Golgi and return to the ER. These sorting signals, or motifs, typically contain the amino acid sequence [[KKXX (amino acid sequence)|KKXX]] or KXKXX, which interact with COPI subunits α-COP and β'-COP.<ref name="KDEL and KKXX retrieval"/><ref name="Ma 926–937"/> The order in which adaptor proteins associate with cargo, or adaptor proteins associate with ARFs is unclear, however, in order to form a mature transport carrier coat protein, adaptor, cargo, and ARF must all associate.

Membrane deformation and carrier budding occurs following the collection of interactions described above. The carrier then buds off of the donor membrane, in the case of COPI this membrane is the cis-Golgi, and the carrier moves to the ER where it fuses with the acceptor membrane and its content is expelled.

== Structure ==
[[File:The_structure_of_the_COPI_triad.png|thumb|396x396px|The COPI triad. Color scheme: membrane - gray; Arf1 - pink; gamma-COP - light green; beta-COP, dark green; zeta-COP - yellow; delta-COP - orange; betaprime-COP - light blue; alpha-COP - dark blue]]
On the surface of a vesicle COPI molecules form symmetric trimers ("triads"). The curved triad structure positions the Arf1 molecules and cargo binding sites proximal to the membrane.  The β′- and α-COP subunits form an arch over the γζβδ-COP subcomplex, orienting their N-terminal domains such that the K(X)KXX cargo-motif binding sites are optimally positioned against the membrane. Thus β′- and α-COP do not form a cage or lattice as in COPII and clathrin coats as previously suggested;<ref>{{Cite journal|last1=Lee|first1=Changwook|last2=Goldberg|first2=Jonathan|date=2010-07-09|title=Structure of coatomer cage proteins and the relationship among COPI, COPII, and clathrin vesicle coats|journal=Cell|volume=142|issue=1|pages=123–132|doi=10.1016/j.cell.2010.05.030|issn=1097-4172|pmc=2943847|pmid=20579721}}</ref> instead, they are linked to one another via the γζβδ-COP subcomplexes, forming an [https://d2ufo47lrtsv5s.cloudfront.net/content/sci/349/6244/195/F1.large.jpg?width=800&height=600&carousel=1 interconnected assembly].<ref>{{Cite journal|last1=Dodonova|first1=S. O.|last2=Diestelkoetter-Bachert|first2=P.|last3=von Appen|first3=A.|last4=Hagen|first4=W. J. H.|last5=Beck|first5=R.|last6=Beck|first6=M.|last7=Wieland|first7=F.|last8=Briggs|first8=J. a. G.|date=2015-07-10|title=VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly|journal=Science|volume=349|issue=6244|pages=195–198|doi=10.1126/science.aab1121|issn=1095-9203|pmid=26160949|s2cid=42823630}}</ref> The triads are linked together with contacts of variable valence making up four different types of contacts.<ref>{{Cite journal|last1=Faini|first1=Marco|last2=Prinz|first2=Simone|last3=Beck|first3=Rainer|last4=Schorb|first4=Martin|last5=Riches|first5=James D.|last6=Bacia|first6=Kirsten|last7=Brügger|first7=Britta|last8=Wieland|first8=Felix T.|last9=Briggs|first9=John A. G.|date=2012-06-15|title=The structures of COPI-coated vesicles reveal alternate coatomer conformations and interactions|journal=Science|volume=336|issue=6087|pages=1451–1454|doi=10.1126/science.1221443|issn=1095-9203|pmid=22628556|bibcode=2012Sci...336.1451F|s2cid=45327176|url=https://eprints.qut.edu.au/57660/1/Faini_galley.pdf}}</ref>

==See also==
*[[Clathrin-coated vesicles]] 
*[[Glyceraldehyde 3-phosphate dehydrogenase#ER-to-Golgi transport|ER-to-Golgi transport]]
*[[Exomer]]

==References==
{{Reflist|2}}<!--added above External links/Sources by script-assisted edit-->

{{Vesicular transport proteins}}

[[Category:Cell biology]]