title: Serial femtosecond crystallography of G protein-coupled receptors.
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.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Daniel
authors.initials: D
authors.lastname: Wacker
authors.forename: Cornelius
authors.initials: C
authors.lastname: Gati
authors.forename: Gye Won
authors.initials: GW
authors.lastname: Han
authors.forename: Daniel
authors.initials: D
authors.lastname: James
authors.forename: Dingjie
authors.initials: D
authors.lastname: Wang
authors.forename: Garrett
authors.initials: G
authors.lastname: Nelson
authors.forename: Uwe
authors.initials: U
authors.lastname: Weierstall
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Katritch
authors.forename: Anton
authors.initials: A
authors.lastname: Barty
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Zatsepin
authors.forename: Dianfan
authors.initials: D
authors.lastname: Li
authors.forename: Marc
authors.initials: M
authors.lastname: Messerschmidt
authors.forename: Sébastien
authors.initials: S
authors.lastname: Boutet
authors.forename: Garth J
authors.initials: GJ
authors.lastname: Williams
authors.forename: Jason E
authors.initials: JE
authors.lastname: Koglin
authors.forename: M Marvin
authors.initials: MM
authors.lastname: Seibert
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Syed T A
authors.initials: ST
authors.lastname: Shah
authors.forename: Shibom
authors.initials: S
authors.lastname: Basu
authors.forename: Raimund
authors.initials: R
authors.lastname: Fromme
authors.forename: Christopher
authors.initials: C
authors.lastname: Kupitz
authors.forename: Kimberley N
authors.initials: KN
authors.lastname: Rendek
authors.forename: Ingo
authors.initials: I
authors.lastname: Grotjohann
authors.forename: Petra
authors.initials: P
authors.lastname: Fromme
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kirian
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Beyerlein
authors.forename: Thomas A
authors.initials: TA
authors.lastname: White
authors.forename: Henry N
authors.initials: HN
authors.lastname: Chapman
authors.forename: Martin
authors.initials: M
authors.lastname: Caffrey
authors.forename: John C H
authors.initials: JC
authors.lastname: Spence
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
authors.forename: Vadim
authors.initials: V
authors.lastname: Cherezov
mesh_terms: D018360:Crystallography, X-Ray / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D007834:Lasers; D011487:Protein Conformation; D044403:Receptor, Serotonin, 5-HT2B / Q000737:chemistry / Q000528:radiation effects; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000528:radiation effects; D013997:Time Factors
chemical_list: D044403:Receptor, Serotonin, 5-HT2B; D043562:Receptors, G-Protein-Coupled