{{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 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 diseases.<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 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 cells. 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 channels. 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 inhibits protein kinase C, Ca<sup>2+</sup>/calmodulin-dependent protein kinase II, myosin light chain kinase, and Na<sup>+</sup>/K<sup>+</sup>-ATPase (synaptosomal membrane). Melittin blocks 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 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 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, but there is no scientific evidence to support the safety or efficacy of any such treatments.<ref name=cass>{{cite book |last1=Barry R. |first1=Cassileth |author-link=Barrie R. Cassileth |title=The Complete Guide to Complementary Therapies in Cancer Care: Essential Information for Patients, Survivors and Health Professionals |chapter-url=https://books.google.com/books?id=J6kLNKw5baYC&pg=PA221 |year=2011 |publisher=World Scientific |isbn=978-981-4335-66-9 |pages=221–224 |chapter=Chapter 36: Apitherapy}}</ref><ref name=acs>{{cite book |publisher=American Cancer Society |title=American Cancer Society Complete Guide to Complementary and Alternative Cancer Therapies |pages=704–708 |chapter=Apitherapy |edition=2nd |year=2009 |isbn=978-0-944235-71-3 |editor1=Russell J |editor2=Rovere A}}</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