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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Javitch, Jonathan A. Guo, Wen Shi, Lei Weinstein, Harel Filizola, Marta |
| Description | Author Affiliation: Guo W ( Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.); |
| Abstract | Functional crosstalk between G protein-coupled receptors in a homo- or heterodimeric assembly likely involves conformational changes at the dimer interface, but the nature of this interface is not yet established, and the dynamic changes have not yet been identified. We have mapped the homodimer interface in the dopamine D2 receptor over the entire length of the fourth transmembrane segment (TM4) by crosslinking of substituted cysteines. Their susceptibilities to crosslinking are differentially altered by the presence of agonists and inverse agonists. The TM4 dimer interface in the inverse agonist-bound conformation is consistent with the dimer of the inactive form of rhodopsin modeled with constraints from atomic force microscopy. Crosslinking of a different set of cysteines in TM4 was slowed by inverse agonists and accelerated in the presence of agonists; crosslinking of the latter set locks the receptor in an active state. Thus, a conformational change at the TM4 dimer interface is part of the receptor activation mechanism. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Models, Molecular Receptors, Dopamine D2 Genetics Metabolism Cross-Linking Reagents Pharmacology Cyclic AMP Dimerization Guanosine 5'-O-(3-Thiotriphosphate) Immunoblotting Mercuric Chloride Mutagenesis, Site-Directed Phenanthrolines Agonists Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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