Multiple Switches in G Protein-Coupled Receptor Activation

被引:98
作者
Ahuja, Shivani
Smith, Steven O. [1 ]
机构
[1] SUNY Stony Brook, Dept Phys & Astron, Stony Brook, NY 11794 USA
基金
美国国家卫生研究院;
关键词
2ND EXTRACELLULAR LOOP; CRYSTAL-STRUCTURE; RHODOPSIN ACTIVATION; PARTIAL AGONISTS; CONSTITUTIVE ACTIVATION; TRANSMEMBRANE HELICES; RETINAL CHROMOPHORE; ANTAGONIST BINDING; STRUCTURAL BASIS; RESIDUES;
D O I
10.1016/j.tips.2009.06.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The activation mechanism of G protein-coupled receptors has presented a puzzle that finally may be close to solution. These receptors have a relatively simple architecture consisting of seven transmembrane helices that contain just a handful of highly conserved amino acids, yet they respond to light and a range of chemically diverse ligands. Recent NMR structural studies on the active metarhodopsin II intermediate of the visual receptor rhodopsin, along with the recent crystal structure of the apoprotein opsin, have revealed multiple structural elements or 'switches' that must be simultaneously triggered to achieve full activation. The confluence of several required structural changes is an example of "coincidence counting", which is often used by nature to regulate biological processes. In ligand-activated G protein-coupled receptors, the presence of multiple switches may provide an explanation for the differences between full, partial and inverse agonists.
引用
收藏
页码:494 / 502
页数:9
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