2. Academic Validation
  3. Serial femtosecond crystallography of G protein-coupled receptors

Serial femtosecond crystallography of G protein-coupled receptors

  • Science. 2013 Dec 20;342(6165):1521-4. doi: 10.1126/science.1244142.
Wei Liu 1,  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
Affiliations

Affiliation

  • 1 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
PMID: 24357322 DOI: 10.1126/science.1244142
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.

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