Serial femtosecond crystallography of G-protein coupled receptors
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Abstract
X-ray crystallography of G protein–coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage and yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) with individual 50-femtosecond-duration x-ray pulses to minimize radiation damage and obtained a high-resolution room-temperature structure of a human serotonin receptor using sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as lipidic cubic phase. Compared with the structure solved by using traditional microcrystallography from cryo-cooled crystals of about two orders of magnitude larger volume, the room-temperature XFEL structure displays a distinct distribution of thermal motions and conformations of residues that likely more accurately represent the receptor structure and dynamics in a cellular environment.
Authors: Wei Liu, Daniel Wacker, Cornelius Gati, Gye Won Han, Daniel James, Dingjie Wang, Garrett Nelson, Uwe Weierstall, Vsevolod Katritch, Anton Barty, Nadia A. Zatsepin, Dianfan Li, Marc Messerschmidt, Sébastien Boutet, Garth J. Williams, Jason E. Koglin, M. Marvin Seibert, Chong Wang, Syed T. A. Shah, Shibom Basu, Raimund Fromme, Christopher Kupitz, Kimberley N. Rendek, Ingo Grotjohann, Petra Fromme, Richard A. Kirian, Kenneth R. Beyerlein, Thomas A. White, Henry N. Chapman, Martin Caffrey, John C. H. Spence, Raymond C. Stevens, Vadim Cherezov
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