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dc.contributor.authorPeigneur, S.
dc.contributor.authorPrabhaDevi
dc.contributor.authorSeldeslachts, A.
dc.contributor.authorRavichandran, S.
dc.contributor.authorQuinton, L.
dc.contributor.authorTytgat, J.
dc.date.accessioned2019-12-31
dc.date.accessioned2020-02-04T09:38:24Z
dc.date.available2019-09-16
dc.date.available2020-02-04T09:38:24Z
dc.date.issued2019
dc.identifier.citationMarine Drugs, vol.17(9); 2019; Article no: 535
dc.identifier.urihttps://doi.org/10.3390/md17090535
dc.identifier.urihttp://drs.nio.org/drs/handle/2264/8256
dc.description.abstractThe a-Conotoxins are peptide toxins that are found in the venom of marine cone snails and they are potent antagonists of various subtypes of nicotinic acetylcholine receptors (nAChRs). Because nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, nAChR dysfunctions have been implicated in a variety of severe pathologies. We describe the isolation and characterization of ?-conotoxin MilIA, the first conopeptide from the venom of Conus milneedwardsi. The peptide was characterized by electrophysiological screening against several types of cloned nAChRs that were expressed in Xenopus laevis oocytes. MilIA, which is a member of the ?3/5 family, is an antagonist of muscle type nAChRs with a high selectivity for muscle versus neuronal subtype nAChRs. Several analogues were designed and investigated for their activity in order to determine the key epitopes of MilIA. Native MilIA and analogues both showed activity at the fetal muscle type nAChR. Two single mutations (Met9 and Asn10) allowed for MilIA to strongly discriminate between the two types of muscle nAChRs. Moreover, one analogue, MilIA [?1,M2R, M9G, N10K, H11K], displayed a remarkable enhanced potency when compared to native peptide. The key residues that are responsible for switching between muscle and neuronal nAChRs preference were elucidated. Interestingly, the same analogue showed a preference for ?9?10 nAChRs among the neuronal types.
dc.languageen
dc.relation.isreferencedbySCI
dc.rightsOnly the author version of the copright reserved papers uploaded. Contact drs@nio.org for any complaints regarding copyright violations
dc.titleStructure-Function Elucidation of a New ?-Conotoxin, MilIA, from Conus milneedwardsi
dc.typeJournal Article


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