1lxg
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Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)
OverviewOverview
The alpha18-mer peptide, spanning residues 181-198 of the Torpedo, nicotinic acetylcholine receptor alpha1 subunit, contains key binding, determinants for agonists and competitive antagonists. To investigate, whether the alpha18-mer can bind other alpha-neurotoxins besides, alpha-bungarotoxin, we designed a two-dimensional (1)H-(15)N heteronuclear, single quantum correlation experiment to screen four related neurotoxins, for their binding ability to the peptide. Of the four toxins tested, (erabutoxin a, erabutoxin b, LSIII, and alpha-cobratoxin), only, alpha-cobratoxin binds the alpha18-mer to form a 1:1 complex. The NMR, solution structure of the alpha-cobratoxin.alpha18-mer complex was, determined with a backbone root mean square deviation of 1.46 A. In the, structure, alpha-cobratoxin contacts the alpha18-mer at the tips of loop I, and II and through C-terminal cationic residues. The contact zone derived, from the intermolecular nuclear Overhauser effects is in agreement with, recent biochemical data. Furthermore, the structural models support the, involvement of cation-pi interactions in stabilizing the complex. In, addition, the binding screen results suggest that C-terminal cationic, residues of alpha-bungarotoxin and alpha-cobratoxin contribute, significantly to binding of the alpha18-mer. Finally, we present a, structural model for nicotinic acetylcholine receptor-alpha-cobratoxin, interaction by superimposing the alpha-cobratoxin.alpha18-mer complex onto, the crystal structure of the acetylcholine-binding protein (Protein Data, Bank code ).
About this StructureAbout this Structure
1LXG is a Protein complex structure of sequences from Naja kaouthia and Torpedo californica. Full crystallographic information is available from OCA.
ReferenceReference
NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica., Zeng H, Hawrot E, J Biol Chem. 2002 Oct 4;277(40):37439-45. Epub 2002 Jul 19. PMID:12133834
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