View source for Melittin

{{Infobox protein family
| Symbol = Melittin
| Name = Melittin
| image = PDB 2mlt EBI.jpg
| width = 
| caption = Melittin
| Pfam = PF01372
| Pfam_clan =  
| InterPro = IPR002116
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 2mlt
| TCDB = 1.C.18
| OPM family = 151
| OPM protein = 2mlt
| CAZy = 
| CDD = 
}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 414059490
| ImageFile=
| ImageSize=275px
| IUPACName=
| OtherNames=
| Reference=<ref>[https://pubchem.ncbi.nlm.nih.gov/compound/16129627 Melitten - Compound Summary], [[PubChem]].</ref>
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|??}}
| CASNo=20449-79-0
| ChEBI_Ref = {{ebicite|changed|EBI}} 
| ChEBI = 6736
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 412927
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 24VT8NVE75
| PubChem = 16133648
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 17290230
| SMILES = CCC(C)C(C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(Cc2c[nH]c3c2cccc3)C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCC(=O)N)C(=O)NC(CCC(=O)N)C(=O)N)NC(=O)CN
| InChI = 1/C131H229N39O31/c1-23-71(16)102(163-97(176)60-135)122(194)146-62-98(177)148-74(19)109(181)164-100(69(12)13)124(196)160-88(55-65(4)5)116(188)155-84(41-30-33-51-134)115(187)165-101(70(14)15)125(197)161-90(57-67(8)9)118(190)168-106(77(22)173)128(200)169-105(76(21)172)123(195)147-63-99(178)150-92(58-68(10)11)129(201)170-54-36-44-94(170)121(193)149-75(20)108(180)158-89(56-66(6)7)117(189)166-104(73(18)25-3)127(199)162-93(64-171)120(192)159-91(59-78-61-145-80-38-27-26-37-79(78)80)119(191)167-103(72(17)24-2)126(198)157-83(40-29-32-50-133)111(183)154-85(42-34-52-143-130(139)140)112(184)152-82(39-28-31-49-132)110(182)153-86(43-35-53-144-131(141)142)113(185)156-87(46-48-96(137)175)114(186)151-81(107(138)179)45-47-95(136)174/h26-27,37-38,61,65-77,81-94,100-106,145,171-173H,23-25,28-36,39-60,62-64,132-135H2,1-22H3,(H2,136,174)(H2,137,175)(H2,138,179)(H,146,194)(H,147,195)(H,148,177)(H,149,193)(H,150,178)(H,151,186)(H,152,184)(H,153,182)(H,154,183)(H,155,188)(H,156,185)(H,157,198)(H,158,180)(H,159,192)(H,160,196)(H,161,197)(H,162,199)(H,163,176)(H,164,181)(H,165,187)(H,166,189)(H,167,191)(H,168,190)(H,169,200)(H4,139,140,143)(H4,141,142,144)/t71-,72-,73-,74-,75-,76+,77+,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,100-,101-,102-,103-,104-,105-,106-/m0/s1
| InChIKey = VDXZNPDIRNWWCW-JFTDCZMZBB
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C131H229N39O31/c1-23-71(16)102(163-97(176)60-135)122(194)146-62-98(177)148-74(19)109(181)164-100(69(12)13)124(196)160-88(55-65(4)5)116(188)155-84(41-30-33-51-134)115(187)165-101(70(14)15)125(197)161-90(57-67(8)9)118(190)168-106(77(22)173)128(200)169-105(76(21)172)123(195)147-63-99(178)150-92(58-68(10)11)129(201)170-54-36-44-94(170)121(193)149-75(20)108(180)158-89(56-66(6)7)117(189)166-104(73(18)25-3)127(199)162-93(64-171)120(192)159-91(59-78-61-145-80-38-27-26-37-79(78)80)119(191)167-103(72(17)24-2)126(198)157-83(40-29-32-50-133)111(183)154-85(42-34-52-143-130(139)140)112(184)152-82(39-28-31-49-132)110(182)153-86(43-35-53-144-131(141)142)113(185)156-87(46-48-96(137)175)114(186)151-81(107(138)179)45-47-95(136)174/h26-27,37-38,61,65-77,81-94,100-106,145,171-173H,23-25,28-36,39-60,62-64,132-135H2,1-22H3,(H2,136,174)(H2,137,175)(H2,138,179)(H,146,194)(H,147,195)(H,148,177)(H,149,193)(H,150,178)(H,151,186)(H,152,184)(H,153,182)(H,154,183)(H,155,188)(H,156,185)(H,157,198)(H,158,180)(H,159,192)(H,160,196)(H,161,197)(H,162,199)(H,163,176)(H,164,181)(H,165,187)(H,166,189)(H,167,191)(H,168,190)(H,169,200)(H4,139,140,143)(H4,141,142,144)/t71-,72-,73-,74-,75-,76+,77+,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,100-,101-,102-,103-,104-,105-,106-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = VDXZNPDIRNWWCW-JFTDCZMZSA-N
| MeSHName=Melitten
  }}
|Section2={{Chembox Properties
| Formula=C<sub>131</sub>H<sub>229</sub>N<sub>39</sub>O<sub>31</sub>
| MolarMass=2846.46266
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
  }}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
  }}
}}

'''Melittin''' is the main component (40–60% of the dry weight) and the major pain-producing substance of honeybee (''[[Apis mellifera]]'') [[venom]]. Melittin is a basic [[peptide]] consisting of 26 [[amino acids]].<ref name="Chen_2016">{{cite journal | vauthors = Chen J, Guan SM, Sun W, Fu H | title = Melittin, the Major Pain-Producing Substance of Bee Venom | journal = Neuroscience Bulletin | volume = 32 | issue = 3 | pages = 265–272 | year = 2016 | pmid = 26983715 | pmc = 5563768 | doi = 10.1007/s12264-016-0024-y }}</ref>

== Function ==

The principal function of melittin as a component of [[bee venom]] is to cause pain and destruction of tissue of intruders that threaten a beehive.{{cn|date=August 2025}} However, melittin is [[genetic expression|expressed]], not only in the venom gland, but also in other tissues when the bee is infected with various pathogens.{{cn|date=August 2025}} The over-expression of melittin (as well as secapin, another venom molecule) in infected honey bees may indicate that it plays a role in the [[immune response]] of bees to [[infectious disease]]s.<ref>{{cite journal | vauthors = Doublet V, Poeschl Y, Gogol-Döring A, Alaux C, Annoscia D, Aurori C, Barribeau SM, Bedoya-Reina OC, Brown MJ, Bull JC, Flenniken ML, Galbraith DA, Genersch E, Gisder S, Grosse I, Holt HL, Hultmark D, Lattorff HM, Le Conte Y, Manfredini F, McMahon DP, Moritz RF, Nazzi F, Niño EL, Nowick K, van Rij RP, Paxton RJ, Grozinger CM | display-authors = 3 | title = Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens | journal = BMC Genomics | volume = 18 | issue = 1 | pages = 207 | date = March 2017 | pmid = 28249569 | pmc = 5333379 | doi = 10.1186/s12864-017-3597-6 | doi-access = free }}</ref>

== Structure ==

Melittin is a small [[peptide]] with no [[disulfide bridge]]; the ''N''-terminal part of the [[molecule]] is predominantly [[hydrophobic]] and the ''C''-terminal part is [[hydrophilic]] and strongly [[Base (chemistry)|basic]].  In water, it forms a [[tetramer]], but it also can spontaneously integrate itself into cell membranes.<ref name="Terwilliger_1982">{{cite journal | vauthors = Terwilliger TC, Eisenberg D | title = The structure of melittin. II. Interpretation of the structure | journal = The Journal of Biological Chemistry | volume = 257 | issue = 11 | pages = 6016–6022 | year = 1982 | doi = 10.1016/S0021-9258(20)65098-0 | pmid = 7076662 | url = http://www.jbc.org/content/257/11/6016.full.pdf | doi-access = free }}</ref>

== Mechanism of action ==

Injection of melittin into animals and humans causes pain sensations. It has strong surface effects on cell membranes, causing pore formation in [[epithelial]] cells and the destruction of [[red blood cell]]s. Melittin also activates [[nociceptor]] (pain receptor) cells through a variety of mechanisms.<ref name="Chen_2016" />

Melittin can open thermal nociceptor [[TRPV1]] channels via [[cyclooxygenase]] metabolites, resulting in depolarization of nociceptor cells.  The pore-forming effects in cells cause the release of pro-inflammatory cytokines.  It also activates [[G-protein-coupled receptor]]-mediated opening of [[transient receptor potential channel]]s.  Finally, melittin up-regulates the expression of [[Nav1.8]] and [[Nav1.9]] sodium channels in nociceptor cell, causing long-term action-potential firing and pain sensation.<ref name="Chen_2016" />

Melittin [[Enzyme inhibitor|inhibits]] [[protein kinase C]], Ca<sup>2+</sup>/calmodulin-dependent protein [[kinase]] II, [[myosin]] [[light]] [[polymer|chain]] kinase, and Na<sup>+</sup>/K<sup>+</sup>-ATPase (synaptosomal membrane). Melittin [[Channel blocker|block]]s [[transport]] pumps such as the Na<sup>+</sup>-K<sup>+</sup>-ATPase and the H<sup>+</sup>-K<sup>+</sup>-ATPase.<ref name="Chen_2016" />

==Toxicity of a bee sting==
{{See also|Bee sting}}
Melittin is the main compound in bee venom, accounting for its potential [[lethality]],  caused by an [[anaphylaxis|anaphylactic reaction]] in some people.<ref name="drugs">{{cite web |title=Bee venom |url=https://www.drugs.com/npp/bee-venom.html |publisher=Drugs.com |access-date=15 July 2024 |date=2 March 2024}}</ref> At the sites of multiple stings, localized pain, swelling, and [[erythema|skin redness]] occur, and if bees are swallowed, life-threatening swelling of the [[throat]] and respiratory passages may develop.<ref name=drugs/>

==Use ==

[[Bee venom therapy]] has been used in [[traditional medicine]] for treating various disorders,<ref name="Rady_2917">{{cite journal | vauthors = Rady I, Siddiqui IA, Rady M, Mukhtar H | title = Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy | journal = Cancer Letters | volume = 402 | pages = 16–31 | year = 2017 | pmid = 28536009 | pmc = 5682937 | doi = 10.1016/j.canlet.2017.05.010 }}</ref> although its non-specific [[toxicity]] has limited [[scientific research]] on its potential effects.<ref name="Liu_2016">{{cite journal | vauthors = Liu CC, Hao DJ, Zhang Q, An J, Zhao JJ, Chen B, Zhang LL, Yang H | title = Application of bee venom and its main constituent melittin for cancer treatment | journal = Cancer Chemotherapy and Pharmacology | volume = 78 | issue = 6 | pages = 1113–1130 | year = 2016 | pmid = 27677623 | doi = 10.1007/s00280-016-3160-1 | s2cid = 12596298 }}</ref>

==Gallery==
<gallery>
File:"Melittin" from the series "The Building Blocks of Life".jpg|Steel sculpture based on the structure of melittin by [[Julian Voss-Andreae]]
</gallery>

== References ==
{{reflist}}

== External links ==
* {{MeshName|Melitten}}

{{Membrane proteins}}
{{Pore-forming toxins}}

[[Category:Antimicrobial peptides]]
[[Category:Insect immunity]]
[[Category:Insect proteins]]