Loop 3 of short neurotoxin II is an additional interaction site with membrane-bound nicotinic acetylcholine receptor as detected by solid-state NMR spectroscopy

J Mol Biol. 2009 Jul 24;390(4):662-71. doi: 10.1016/j.jmb.2009.05.016. Epub 2009 May 15.

Abstract

The contact area of neurotoxin II from Naja naja oxiana when interacting with the membrane-bound nicotinic acetylcholine receptor from Torpedo californica was determined by solid-state, magic-angle spinning NMR spectroscopy. For this purpose, the carbon signals for more than 90% of the residues of the bound neurotoxin were assigned. Differences between the solution and solid-state chemical shifts of the free and bound form of the toxin are confined to distinct surface regions. Loop II of the short toxin was identified as the main interaction site. In addition, loop III of neurotoxin II shows several strong responses defining an additional interaction site. A comparison with the structures of alpha-cobratoxin bound to the acetylcholine-binding protein from snail species Lymnaea stagnalis and Aplysia californica, and of alpha-bungarotoxin bound to an extracellular domain of an alpha-subunit of the receptor reveals different contact areas for long and short alpha-neurotoxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cobra Neurotoxin Proteins / chemistry*
  • Cobra Neurotoxin Proteins / metabolism
  • In Vitro Techniques
  • Membranes / metabolism
  • Molecular Sequence Data
  • Mollusk Venoms / chemistry
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Conformation
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism
  • Torpedo

Substances

  • Cobra Neurotoxin Proteins
  • Mollusk Venoms
  • Receptors, Nicotinic
  • neurotoxin II, Naja naja oxiana