1LXG: Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)

Citation:
Abstract
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 ).
PDB ID: 1LXGDownload
MMDB ID: 21187
PDB Deposition Date: 2002/6/5
Updated in MMDB: 2002/12
Experimental Method:
solution nmr
Source Organism:
Naja kaouthia
Similar Structures:
Molecular Components in 1LXG
Label Count Molecule
Proteins (2 molecules)
1
Long Neurotoxin 1
Molecule annotation
1
Acetylcholine Receptor Protein, Alpha Chain
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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