Specific Membrane Binding of Neurotoxin II Can Facilitate Its Delivery to Acetylcholine Receptor

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2009 Oct 7

PMID 19804741

Citations 12

Authors

Dmitry M Lesovoy

Eduard V Bocharov

Ekaterina N Lyukmanova

Yurij A Kosinsky

Mikhail A Shulepko

Dmitry A Dolgikh

Mikhail P Kirpichnikov

Roman G Efremov

Alexander S Arseniev

Affiliations

Soon will be listed here.

Abstract

The action of three-finger snake alpha-neurotoxins at their targets, nicotinic acetylcholine receptors (nAChR), is widely studied because of its biological and pharmacological relevance. Most such studies deal only with ligands and receptor models; however, for many ligand/receptor systems the membrane environment may affect ligand binding. In this work we focused on binding of short-chain alpha-neurotoxin II (NTII) from Naja oxiana to the native-like lipid bilayer, and the possible role played by the membrane in delivering the toxin to nAChR. Experimental (NMR and mutagenesis) and molecular modeling (molecular-dynamics simulation) studies revealed a specific interaction of the toxin molecule with the phosphatidylserine headgroup of lipids, resulting in the proper topology of NTII on lipid bilayers favoring the attack of nAChR. Analysis of short-chain alpha-neurotoxins showed that most of them possess a high positive charge and sequence homology in the lipid-binding motif of NTII, implying that interaction with the membrane surrounding nAChR may be common for the toxin family.

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