期刊
NATURE
卷 523, 期 7562, 页码 561-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature14656
关键词
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资金
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- National Institutes of Health [P41GM103393]
- Michigan Economic Development Corporation
- Michigan Technology Tri-Corridor [085P1000817]
- Federal funds from the National Cancer Institute [ACB-12002]
- National Institute of General Medical Sciences [AGM-12006]
- Office of Science of the US Department of Energy [DE-AC02-06CH11357]
- Jay and Betty Van Andel Foundation, Ministry of Science and Technology (China) [2012ZX09301001, 2012CB910403, 2013CB910600, XDB08020303, 2013ZX09507001]
- Amway (China)
- National Institute of Health [DK071662, GM073197, GM103310, GM102545, GM104212, EY011500, GM077561, EY005216, P30EY000331]
- National Institutes of Health Common Fund in Structural Biology grants [P50 GM073197, P50 GM073210, GM095583]
- NSF Science and Technology Center [1231306]
- Swiss National Science Foundation [31003A_141235]
- Canada Excellence Research Chair program
- Anne & Max Tanenbaum Chair in Neuroscience at the University of Toronto
- Science Foundation Ireland [12/IA/1255]
- Helmholtz Gemeinschaft
- DFG Cluster of Excellence Center for Ultrafast Imaging
- BMBF [FKZ 05K12CH1]
- Irene and Eric Simon Brain Research Foundation
- PIER Helmholtz-Graduate School
- Helmholtz Association
- National Institute of General Medical Sciences PSI: Biology grants [U54 GM094618, GM108635, U54 GM094599, GM097463, U54 GM094586]
- Swiss National Science Foundation (SNF) [31003A_141235] Funding Source: Swiss National Science Foundation (SNF)
G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a similar to 20 degrees rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.
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