Please use this identifier to cite or link to this item: https://doi.org/10.1021/bi061969o
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dc.titleProtein folding determinants: Structural features determining alternative disulfide pairing in α- and χ/λ-conotoxins
dc.contributor.authorKang, T.S.
dc.contributor.authorRadić, Z.
dc.contributor.authorTalley, T.T.
dc.contributor.authorJois, S.D.S.
dc.contributor.authorTaylor, P.
dc.contributor.authorKini, R.M.
dc.date.accessioned2014-10-27T08:37:36Z
dc.date.available2014-10-27T08:37:36Z
dc.date.issued2007-03-20
dc.identifier.citationKang, T.S., Radić, Z., Talley, T.T., Jois, S.D.S., Taylor, P., Kini, R.M. (2007-03-20). Protein folding determinants: Structural features determining alternative disulfide pairing in α- and χ/λ-conotoxins. Biochemistry 46 (11) : 3338-3355. ScholarBank@NUS Repository. https://doi.org/10.1021/bi061969o
dc.identifier.issn00062960
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/101476
dc.description.abstractα-Conotoxins isolated from Conus venoms contain 11-19 residues and preferentially fold into the globular conformation that possesses a specific disulfide pairing pattern (C1-3, C2-4). We and others isolated a new family of χ-conotoxins (also called λ conotoxins) with the conserved cysteine framework of α-conotoxins but with alternative disulfide pairing (C1-4, C2-3) resulting in the ribbon conformation. In both families, disulfide pairing and hence folding are important for their biological potency. By comparing the structural differences, we identified potential structural determinants responsible for the folding tendencies of these conotoxins. We examined the role of conserved proline in the first intercysteine loop and the conserved C-terminal amide on folding patterns of synthetic analogues of ImI conotoxin by comparing the isoforms with the regiospecifically synthesized conformers. Deamidation at the C-terminus and substitution of proline in the first intercysteine loop switch the folding pattern from the globular form of α-conotoxins to the ribbon form of γ/λ-conotoxins. The findings are corroborated by reciprocal folding of CMrVIA χ/λ-conotoxins. Substitution of Lys-6 from the first intercysteine loop of CMrVIA conotoxin with proline, as well as the inclusion of an amidated C-terminal shifted the folding preference of CMrVIA conotoxin from its native ribbon conformation toward the globular conformation. Binding assays of ImI conotoxin analogues with Aplysia and Bulinus acetylcholine binding protein indicate that both these substitutions and their consequent conformational change substantially impact the binding affinity of ImI conotoxin. These results strongly indicate that the first intercysteine loop proline and C-terminal amidation act as conformational switches in α- and χ/λ-conotoxins. © 2007 American Chemical Society.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1021/bi061969o
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentPHARMACY
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1021/bi061969o
dc.description.sourcetitleBiochemistry
dc.description.volume46
dc.description.issue11
dc.description.page3338-3355
dc.description.codenBICHA
dc.identifier.isiut000244854800043
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