NMR spatial structure of α‐conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors 1

FEBS Letters

Zhmak, Maxim N¹  Maslennikov, Innokenty V¹  Tsetlin, Victor I¹  Arseniev, Alexander S¹  Methfessel, Christoph²  Shenkarev, Zakhar O¹  Ivanov, Vadim T¹ 

[1] Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, 16/10 Miklukho-Maklaya, Moscow 117871, Russia;Zentrale Forschung, Abteilung Biophysik, Bayer AG, D-51368 Leverkusen, Germany

关键词: Nuclear magnetic resonance structure;    Neurotoxin;    Conotoxin;    Acetylcholine receptor;    α-CTx;    α-conotoxin;    α-NTx;    α-neurotoxin;    nAChR;    nicotinic acetylcholine receptor;    NOE;    nuclear Overhauser enhancement;    NOESY;    2D NOE-correlated spectroscopy;    TOCSY;    2D total correlated spectroscopy;   

DOI  :  10.1016/S0014-5793(99)00069-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown