4NC3 : Crystal structure of the 5-HT2B receptor solved using serial femtosecond crystallography in lipidic cubic phase.

Experimental Technique/Method:X-RAY DIFFRACTION Resolution:2.8 Classification:SIGNALING PROTEIN, ELECTRON TRANSPORT Release Date:2013-12-18 Deposition Date:2013-10-23 Revision Date:2014-01-22#2017-06-07#2018-02-14 Molecular Weight:53259.86 Macromolecule Type:Protein Residue Count:430 Atom Site Count:3116 DOI:10.2210/pdb4nc3/pdb 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.