1KC4

NMR Structural Analysis of the Complex Formed Between alpha-Bungarotoxin and the Principal alpha-Neurotoxin Binding Sequence on the alpha7 Subunit of a Neuronal Nicotinic Acetylcholine Receptor

Summary for 1KC4

• Entry DOI: 10.2210/pdb1kc4/pdb
• Related: 1ABT 1BXP 1HAJ 1HC9 1I9B 1IDH 1IKC 1JBD 1KFH 1KL8 2ABX
• Descriptor: alpha-bungarotoxin, neuronal acetylcholine receptor protein, alpha-7 chain (2 entities in total)
• Functional Keywords: alpha-bungarotoxin, nicotinic acetylcholine receptor alpha 7 subunit, alpha-neurotoxin, ligand-gated ion channels, protein-protein interactions, protein-peptide complex, toxin
• Biological source: Gallus gallus (chicken); More
• Cellular location: Secreted: P60615; Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P22770
• Total number of polymer chains: 2
• Total formula weight: 10353.91

Authors

Moise, L.,Piserchio, A.,Basus, V.J.,Hawrot, E. (deposition date: 2001-11-07, release date: 2002-03-13, Last modification date: 2021-10-27)

Primary citation

Moise, L.,Piserchio, A.,Basus, V.J.,Hawrot, E.
NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor.
J.Biol.Chem., 277:12406-12417, 2002

PubMed Abstract: We report a new, higher resolution NMR structure of alpha-bungarotoxin that defines the structure-determining disulfide core and beta-sheet regions. We further report the NMR structure of the stoichiometric complex formed between alpha-bungarotoxin and a recombinantly expressed 19-mer peptide ((178)IPGKRTESFYECCKEPYPD(196)) derived from the alpha7 subunit of the chick neuronal nicotinic acetylcholine receptor. A comparison of these two structures reveals binding-induced stabilization of the flexible tip of finger II in alpha-bungarotoxin. The conformational rearrangements in the toxin create an extensive binding surface involving both sides of the alpha7 19-mer hairpin-like structure. At the contact zone, Ala(7), Ser(9), and Ile(11) in finger I and Arg(36), Lys(38), Val(39), and Val(40) in finger II of alpha-bungarotoxin interface with Phe(186), Tyr(187), Glu(188), and Tyr(194) in the alpha7 19-mer underscoring the importance of receptor aromatic residues as critical neurotoxin-binding determinants. Superimposing the structure of the complex onto that of the acetylcholine-binding protein (1I9B), a soluble homologue of the extracellular domain of the alpha7 receptor, places alpha-bungarotoxin at the peripheral surface of the inter-subunit interface occluding the agonist-binding site. The disulfide-rich core of alpha-bungarotoxin is suggested to be tilted in the direction of the membrane surface with finger II extending into the proposed ligand-binding cavity.

PubMed: 11790782
DOI: 10.1074/jbc.M110320200

Experimental method

SOLUTION NMR