Crystal structure of oligomeric β1-adrenergic G protein-coupled receptors in ligand-free basal state.

Crystal structure of oligomeric β1-adrenergic G protein-coupled receptors in ligand-free basal state.
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DOI:
10.1038/nsmb.2504
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发表时间:
2013-04
影响因子:
16.8
通讯作者:
Huang, Xin-Yun
Huang, Xin-Yun
中科院分区:
生物学1区
文献类型:
--
作者:
Huang, Jianyun;Chen, Shuai;Zhang, J. Jillian;Huang, Xin-Yun

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G protein-coupled receptors (GPCRs) mediate transmembrane signaling. Before ligand binding, GPCRs exist in a basal state. Crystal structures of several GPCRs bound with antagonists or agonists have been solved. However, the crystal structure of the ligand-free basal state of a GPCR, the starting point of GPCR activation and function, has not been determined. Here we report the X-ray crystal structure of the first ligand-free basal state of a GPCR in a lipid membrane-like environment. Oligomeric turkey β1-adrenergic receptors display two alternating dimer interfaces. One interface involves the transmembrane domain (TM) 1, TM2, the C-terminal H8, and the extracellular loop 1. The other interface engages residues from TM4, TM5, the intracellular loop 2 and the extracellular loop 2. Structural comparisons show that this ligand-free state is in an inactive conformation. This provides the structural information regarding GPCR dimerization and oligomerization.
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