2br8 is a 10 chain structure with sequence from Aplca. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[CA1A_CONPE] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4).[1][2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Conotoxins (Ctx) form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors. The subgroup alpha-Ctx specifically and selectively binds to subtypes of nicotinic acetylcholine receptors (nAChRs), which are targets for treatment of several neurological disorders. Here we present the structure at a resolution of 2.4 A of alpha-Ctx PnIA (A10L D14K), a potent blocker of the alpha(7)-nAChR, bound with high affinity to acetylcholine binding protein (AChBP), the prototype for the ligand-binding domains of the nAChR superfamily. Alpha-Ctx is buried deep within the ligand-binding site and interacts with residues on both faces of adjacent subunits. The toxin itself does not change conformation, but displaces the C loop of AChBP and induces a rigid-body subunit movement. Knowledge of these contacts could facilitate the rational design of drug leads using the Ctx framework and may lead to compounds with increased receptor subtype selectivity.
Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant.,Celie PH, Kasheverov IE, Mordvintsev DY, Hogg RC, van Nierop P, van Elk R, van Rossum-Fikkert SE, Zhmak MN, Bertrand D, Tsetlin V, Sixma TK, Smit AB Nat Struct Mol Biol. 2005 Jul;12(7):582-8. Epub 2005 Jun 12. PMID:15951818[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Luo S, Nguyen TA, Cartier GE, Olivera BM, Yoshikami D, McIntosh JM. Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity. Biochemistry. 1999 Nov 2;38(44):14542-8. PMID:10545176
↑Fainzilber M, Hasson A, Oren R, Burlingame AL, Gordon D, Spira ME, Zlotkin E. New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors. Biochemistry. 1994 Aug 16;33(32):9523-9. PMID:8068627
↑Celie PH, Kasheverov IE, Mordvintsev DY, Hogg RC, van Nierop P, van Elk R, van Rossum-Fikkert SE, Zhmak MN, Bertrand D, Tsetlin V, Sixma TK, Smit AB. Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant. Nat Struct Mol Biol. 2005 Jul;12(7):582-8. Epub 2005 Jun 12. PMID:15951818 doi:10.1038/nsmb951
