Source:http://linkedlifedata.com/resource/pubmed/id/11790782
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
14
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| pubmed:dateCreated |
2002-4-1
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| pubmed:databankReference | |
| pubmed:abstractText |
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.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Bungarotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
5
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| pubmed:volume |
277
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
12406-17
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11790782-Amino Acid Sequence,
pubmed-meshheading:11790782-Amino Acids,
pubmed-meshheading:11790782-Animals,
pubmed-meshheading:11790782-Binding Sites,
pubmed-meshheading:11790782-Bungarotoxins,
pubmed-meshheading:11790782-Chickens,
pubmed-meshheading:11790782-Disulfides,
pubmed-meshheading:11790782-Kinetics,
pubmed-meshheading:11790782-Ligands,
pubmed-meshheading:11790782-Magnetic Resonance Spectroscopy,
pubmed-meshheading:11790782-Models, Molecular,
pubmed-meshheading:11790782-Molecular Sequence Data,
pubmed-meshheading:11790782-Neurons,
pubmed-meshheading:11790782-Peptides,
pubmed-meshheading:11790782-Protein Binding,
pubmed-meshheading:11790782-Protein Conformation,
pubmed-meshheading:11790782-Protein Structure, Secondary,
pubmed-meshheading:11790782-Protein Structure, Tertiary,
pubmed-meshheading:11790782-Receptors, Nicotinic,
pubmed-meshheading:11790782-Sequence Homology, Amino Acid
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| pubmed:year |
2002
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| pubmed:articleTitle |
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.
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| pubmed:affiliation |
Department of Molecular Pharmacology, Brown University, Providence, Rhode Island 02912, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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