Database Accession: DI1110016
Name: Alpha-bungarotoxin complexed with a cognate peptide from acetylcholine receptor protein, alpha chain
PDB ID: 1abt
Experimental method: NMR
Source organism: Torpedo californica / Bungarus multicinctus
Proof of disorder:
Kd: 6.50×10-08 M
Primary publication of the structure:
Basus VJ, Song G, Hawrot E
NMR solution structure of an alpha-bungarotoxin/nicotinic receptor peptide complex.
(1993) Biochemistry 32: 12290-8
PMID: 8241115
Abstract:
We report the two-dimensional nuclear magnetic resonance (NMR) characterization of the stoichiometric complex formed between the snake venom-derived long alpha-neurotoxin, alpha-bungarotoxin (BGTX), and a synthetic dodecapeptide (alpha 185-196) corresponding to a functionally important region on the alpha-subunit of the nicotinic acetylcholine receptor (nAChR) obtained from Torpedo californica electric organ tissue. BGTX has been widely used as the classic nicotinic competitive antagonist for the skeletal muscle type of nAChR which is found in the avian, amphibian, and mammalian neuromuscular junction. The receptor dodecapeptide (alpha 185-196) binds BGTX with micromolar affinity and has been shown to represent the major determinant of BGTX binding to the isolated alpha-subunit. Previous studies involving covalent modification of the native nAChR from Torpedo membranes with a variety of affinity reagents indicate that several residues contained within the dodecapeptide sequence (namely, Tyr-190, Cys-192, and Cys-193) apparently contribute directly to the formation of the cholinergic ligand binding site. The NMR-derived solution structure of the BGTX/receptor peptide complex defines a relatively extended conformation for a major segment of the "bound" dodecapeptide. These structural studies also reveal a previously unpredicted receptor binding cleft within BGTX and suggest that BGTX undergoes a conformational change upon peptide binding. If, as we hypothesize, the identified intermolecular contacts in the BGTX/receptor peptide complex describe a portion of the contact zone between BGTX and native receptor, then the structural data would suggest that alpha-subunit residues 186-190 are on the extracellular surface of the receptor.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
Biological process: not assigned
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: B, A
Notes: No modifications of the original PDB file.
Name: Acetylcholine receptor subunit alpha
Source organism: Torpedo californica
Length: 12 residues
Sequence:Sequence according to PDB SEQRESKHWVYYTCCPDT
UniProtKB AC: P02710 (positions: 209-220) Coverage: 2.6%
UniRef90 AC: UniRef90_P02710 (positions: 209-220)
Name: Alpha-bungarotoxin isoform A31
Source organism: Bungarus multicinctus
Length: 74 residues
Sequence:Sequence according to PDB SEQRESIVCHTTATSPISAVTCPPGENLCYRKMWCDAFCSSRGKVVELGCAATCPSKKPYEEVTCCSTDKCNPHPKQRPG
UniProtKB AC: P60615 (positions: 22-95) Coverage: 77.9%
UniRef90 AC: UniRef90_P60615 (positions: 22-95)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Chain B:
The interacting region of acetylcholine receptor alpha1 subunit hsa been shown to be unstructured in its unbound form (PMID: 12133834).
Chain A:
The snake toxin domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00087). A solved monomeric structure of the domain is represented by PDB ID 1idi.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). The structure can be rotated by left click and hold anywhere on the structure. Representation options can be edited by right clicking on the structure window.
