Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser
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- Van Andel Research Inst. (VARI), Grand Rapids, MI (United States)
- Arizona State Univ., Tempe, AZ (United States). Biodesign Inst., Dept. of Chemistry and Biochemistry
- Univ. of Southern California, Los Angeles, CA (United States). Bridge Inst., Dept. of Chemistry
- Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Center for Free-Electron Laser Science
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL), Joint Center for Structural Genomics
- Van Andel Research Inst. (VARI), Grand Rapids, MI (United States); National Univ. of Singapore (Singapore). Yong Loo Lin School of Medicine, Dept. of Obstetrics & Gynecology
- New York Structural Biology Center (NYSBC), New York, NY (United States)
- Scripps Research Inst., Jupiter, FL (United States). Dept. of Molecular Therapeutics
- Univ. of California, Los Angeles, CA (United States). Jules Stein Eye Inst.
- Univ. of Toronto, ON (Canada). Dept. of Biochemistry
- Vanderbilt Univ., Nashville, TN (United States). Dept. of Pharmacology
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS); NSF Science and Technology Center, Buffalo, NY (United States). BioXFEL
- Arizona State Univ., Tempe, AZ (United States). Biodesign Inst., Dept. of Chemistry and Biochemistry; Arizona State Univ., Tempe, AZ (United States). Dept. of Physics
- Arizona State Univ., Tempe, AZ (United States). Biodesign Inst., Dept. of Chemistry and Biochemistry; Beijing Computational Science Research Center, Beijing (China)
- Arizona State Univ., Tempe, AZ (United States). Biodesign Inst., Dept. of Chemistry and Biochemistry; Univ. of Wisconsin-Milwaukee, Milwaukee, WI (United States). Dept. of Physics
- Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Materia Medica, State Key Lab. of Drug Research
- National Univ. of Singapore (Singapore). Yong Loo Lin School of Medicine, Dept. of Obstetrics & Gynecology
- Paul Scherrer Inst. (PSI), Villigen (Switzerland). Swiss Light Source
- Univ. of Southern California, Los Angeles, CA (United States). Bridge Inst., Dept. of Biological Sciences
- Trinity College, Dublin, (Ireland). School of Medicine and School of Biochemistry and Immunology
- NSF Science and Technology Center, Buffalo, NY (United States). BioXFEL; Univ. of Chicago, IL (United States). Ben May Dept. for Cancer Research
- Paul Scherrer Inst., Villigen (Switzerland). Lab. of Biomolecular Research
- Univ. of Konstanz, Konstanz (Germany). Dept. of Biology
- Chinese Academy of Sciences (CAS), Beijing (China). Inst. of High Energy Physics, Beijing Synchrotron Radiation Facility
- Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Center for Free-Electron Laser Science; Centre for Ultrafast Imaging, Hamburg (Germany)
- Univ. of Toronto, ON (Canada). Dept. of Biochemistry; Univ. of Toronto, ON (Canada). Dept. of Molecular Genetics
- Univ. of Southern California, Los Angeles, CA (United States). Bridge Inst., Dept. of Chemistry; Univ. of Southern California, Los Angeles, CA (United States). Bridge Inst., Dept. of Biological Sciences; ShanghaiTech Univ., Shanghai (China)
- Van Andel Research Inst. (VARI), Grand Rapids, MI (United States); Chinese Academy of Sciences (CAS), Shanghai (China). Shanghai Inst. of Materia Medica
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 ~20° 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. In conclusion, 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.
- Research Organization:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH)
- Grant/Contract Number:
- AC02-76SF00515; AC02-06CH11357
- OSTI ID:
- 1260958
- Alternate ID(s):
- OSTI ID: 1259890
- Journal Information:
- Nature (London), Journal Name: Nature (London) Journal Issue: 7562 Vol. 523; ISSN 0028-0836
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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