Dimer-based model for heptaspanning membrane receptors

被引:54
作者
Franco, R
Casadó, V
Mallol, J
Ferré, S
Fuxe, K
Cortés, A
Ciruela, F
Lluis, C
Canela, EI
机构
[1] Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain
[2] NIDA, US Dept HHS, NIH, Baltimore, MD 21224 USA
[3] Karolinska Inst, KF, Div Cellular & Mol Neurochem, Dept Neurosci, S-17177 Stockholm, Sweden
关键词
D O I
10.1016/j.tibs.2005.05.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dinners as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.
引用
收藏
页码:360 / 366
页数:7
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