2i28
From Proteopedia
Solution Structure of alpha-Conotoxin BuIA
Structural highlights
FunctionCA1A_CONBU Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This peptide potently blocks numerous mammalian nAChR subtypes (alpha-6 or -3/beta-2 or -3 > alpha-6 or-3/beta-4 > alpha-3/beta-2 > alpha-3/beta-4 > alpha-4/beta-4 = alpha-2/beta-4 > alpha-7 > alpha-2/beta-2 >> alpha-4/beta-2). Recovery from toxin block is markedly slower for beta-4 versus beta-2 subunit-containing nAChRs. Thus, it represents a novel probe for distinguishing between beta-2 and beta-4-containing nAChRs. Publication Abstract from PubMedWe have determined a high-resolution three-dimensional structure of alpha-conotoxin BuIA, a 13-residue peptide toxin isolated from Conus bullatus. Despite its unusual 4/4 disulfide bond layout alpha-conotoxin BuIA exhibits strong antagonistic activity at alpha6/alpha3beta2beta3, alpha3beta2, and alpha3beta4 nAChR subtypes like some alpha4/7 conotoxins. alpha-Conotoxin BuIA lacks the C-terminal beta-turn present within the second disulfide loop of alpha4/7 conotoxins, having only a "pseudo omega-shaped" molecular topology. Nevertheless, it contains a functionally critical two-turn helix motif, a feature ubiquitously found in alpha4/7 conotoxins. Such an aspect seems mainly responsible for similarities in the receptor recognition profile of alpha-conotoxin BuIA to alpha4/7 conotoxins. Structural comparison of alpha-conotoxin BuIA with alpha4/7 conotoxins and alpha4/3 conotoxin ImI suggests that presence of the second helical turn portion of the two-turn helix motif in alpha4/7 and alpha4/4 conotoxins may be important for binding to the alpha3 and/or alpha6 subunit of nAChR. NMR structure determination of alpha-conotoxin BuIA, a novel neuronal nicotinic acetylcholine receptor antagonist with an unusual 4/4 disulfide scaffold.,Chi SW, Kim DH, Olivera BM, McIntosh JM, Han KH Biochem Biophys Res Commun. 2006 Nov 3;349(4):1228-34. Epub 2006 Sep 7. PMID:16979596[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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