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NMR spatial structure of α‐conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors 1
Author(s) -
Maslennikov Innokenty V,
Shenkarev Zakhar O,
Zhmak Maxim N,
Ivanov Vadim T,
Methfessel Christoph,
Tsetlin Victor I,
Arseniev Alexander S
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00069-1
Subject(s) - nicotinic acetylcholine receptor , conotoxin , acetylcholine receptor , snail , nicotinic agonist , acetylcholine , chemistry , neuroscience , receptor , biology , biochemistry , pharmacology , ecology , venom
A 600 MHz NMR study of α‐conotoxin ImI from Conus imperialis , targeting the α7 neuronal nicotinic acetylcholine receptor (nAChR), is presented. ImI backbone spatial structure is well defined basing on the NOEs, spin‐spin coupling constants, and amide protons hydrogen‐deuterium exchange data: rmsd of the backbone atom coordinates at the 2–12 region is 0.28 Å in the 20 best structures. The structure is described as a type I β‐turn (positions 2–5) followed bya distorted helix (positions 5–11). Similar structural psattern can be found in all neuronal‐specific α‐conotoxins. Highly mobile side chains of the Asp‐5, Arg‐7 and Trp‐10 residues form a single site for ImI binding to the α7 receptor. When depicted with opposite directions of the polypeptide chains, the ImI helix and the tip of the central loop of long chain snake neurotoxins demonstrate a common scaffold and similar positioning of the functional side chains, both of these structural elements appearing essential for binding to the neuronal nAChRs.