1LXG

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

Summary for 1LXG

• Entry DOI: 10.2210/pdb1lxg/pdb
• Related: 1lxh
• Descriptor: Long neurotoxin 1, Acetylcholine receptor protein, alpha chain (2 entities in total)
• Functional Keywords: toxin, alpha-cobratoxin, nicotinic acetylcholine receptor, protein-protein interaction
• Biological source: Torpedo californica (Pacific electric ray); More
• Cellular location: Secreted: P01391; Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P02710
• Total number of polymer chains: 2
• Total formula weight: 10266.83

Authors

Zeng, H.,Hawrot, E. (deposition date: 2002-06-05, release date: 2002-11-20, Last modification date: 2022-02-23)

Primary citation

Zeng, H.,Hawrot, E.
NMR-based Binding Screen and Structural Analysis of the Complex Formed between alpha-Cobratoxin and an 18-mer Cognate Peptide Derived from the alpha1 Subunit of the Nicotinic Acetylcholine Receptor from Torpedo californica
J.Biol.Chem., 277:37439-37445, 2002

PubMed 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 ).

PubMed: 12133834
DOI: 10.1074/jbc.M205483200

Experimental method

SOLUTION NMR