Serial femtosecond crystallography of G protein-coupled receptors Academic Article uri icon


  • 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.


  • Liu, W
  • Wacker, D
  • Gati, C
  • Han, GW
  • James, D
  • Wang, D
  • Nelson, G
  • Weierstall, U
  • Katritch, V
  • Barty, A
  • Zatsepin, Nadia A
  • Li, D
  • Messerschmidt, M
  • Boutet, S
  • Williams, GJ
  • Koglin, JE
  • Seibert, MM
  • Wang, C
  • Shah, STA
  • Basu, S
  • Fromme, R
  • Kupitz, C
  • Rendek, KN
  • Grotjohann, I
  • Fromme, P
  • Kirian, RA
  • Beyerlein, KR
  • White, TA
  • Chapman, HN
  • Caffrey, M
  • Spence, JCH
  • Stevens, RC
  • Cherezov, V

publication date

  • 2013