Source:http://linkedlifedata.com/resource/pubmed/id/12556472
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
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| pubmed:dateCreated |
2003-4-7
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| pubmed:abstractText |
The GABA-binding site undergoes structural rearrangements during the transition from agonist binding to channel opening. To define possible roles of the GABA(A) receptor alpha(1) subunit Pro(174)-Asp(191) segment in these processes, we used the substituted cysteine accessibility method to characterize this region. Each residue was individually mutated to cysteine, expressed with wild-type beta(2) subunits in Xenopus laevis oocytes, and examined using two-electrode voltage clamp. Most mutations did not alter GABA EC(50) values. The D183C mutation produced a 7-fold reduction in GABA sensitivity. There were no significant changes in the K(I) values for the competitive antagonist, SR-95531. N-Biotinylaminoethyl methanethiosulfonate modified P174C-, R176C-, S177C-, V178C-, V180C-, A181C-, D183C-, R186C- and N188C-containing receptors. The pattern of accessibility suggests that this protein segment is aqueous-exposed and adopts a random coil conformation. Both GABA and SR-95531 slowed covalent modification of V178C, V180C, and D183C, indicating that these residues may line the GABA-binding site. Further, pentobarbital-induced channel activation accelerated modification of V180C and A181C and slowed the modification of R186C, suggesting that this region of the alpha(1) subunit may act as a dynamic element during channel-gating transitions.
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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/Pentobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
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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 |
11
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| pubmed:volume |
278
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
13166-72
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12556472-Amino Acid Sequence,
pubmed-meshheading:12556472-Amino Acid Substitution,
pubmed-meshheading:12556472-Animals,
pubmed-meshheading:12556472-Binding Sites,
pubmed-meshheading:12556472-Ion Channel Gating,
pubmed-meshheading:12556472-Kinetics,
pubmed-meshheading:12556472-Models, Molecular,
pubmed-meshheading:12556472-Molecular Sequence Data,
pubmed-meshheading:12556472-Mutagenesis, Site-Directed,
pubmed-meshheading:12556472-Patch-Clamp Techniques,
pubmed-meshheading:12556472-Pentobarbital,
pubmed-meshheading:12556472-Peptide Fragments,
pubmed-meshheading:12556472-Protein Conformation,
pubmed-meshheading:12556472-Protein Subunits,
pubmed-meshheading:12556472-Rats,
pubmed-meshheading:12556472-Receptors, GABA-A,
pubmed-meshheading:12556472-Sequence Alignment,
pubmed-meshheading:12556472-Sequence Homology, Amino Acid,
pubmed-meshheading:12556472-gamma-Aminobutyric Acid
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| pubmed:year |
2003
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| pubmed:articleTitle |
The GABAA receptor alpha 1 subunit Pro174-Asp191 segment is involved in GABA binding and channel gating.
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| pubmed:affiliation |
Department of Physiology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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