@article{a911d47ddccf4c718d4a5ae89a9dc0e8,
title = "Native phasing of x-ray free-electron laser data for a G protein–coupled receptor",
abstract = "Serial femtosecond crystallography (SFX) takes advantage of extremely bright and ultrashort pulses produced by x-ray free-electron lasers (XFELs), allowing for the collection of high-resolution diffraction intensities from micrometer-sized crystals at room temperature with minimal radiation damage, using the principle of “diffraction-before-destruction.” However, de novo structure factor phase determination using XFELs has been difficult so far. We demonstrate the ability to solve the crystallographic phase problem for SFX data collected with an XFEL using the anomalous signal from native sulfur atoms, leading to a bias-free room temperature structure of the human A2A adenosine receptor at 1.9 {\AA} resolution. The advancement was made possible by recent improvements in SFX data analysis and the design of injectors and delivery media for streaming hydrated microcrystals. This general method should accelerate structural studies of novel difficult-to-crystallize macromolecules and their complexes.",
author = "Alexander Batyuk and Lorenzo Galli and Andrii Ishchenko and Han, {Gye Won} and Cornelius Gati and Popov, {Petr A.} and Lee, {Ming Yue} and Benjamin Stauch and White, {Thomas A.} and Anton Barty and Andrew Aquila and Hunter, {Mark S.} and Mengning Liang and S{\'e}bastien Boutet and Mengchen Pu and Liu, {Zhi jie} and Garrett Nelson and Daniel James and Chufeng Li and Yun Zhao and John Spence and Wei Liu and Petra Fromme and Vsevolod Katritch and Uwe Weierstall and Stevens, {Raymond C.} and Vadim Cherezov",
note = "Funding Information: We thank A. Walker for assistance with manuscript preparation. A. Batyuk thanks A. Pl{\"u}ckthun for helpful discussions. This work was supported by NIH grants R01 GM108635 (V.C.), U54 GM094618 (V.C., V.K., and R.C.S.), U54 GM094599 (P.F.), and R01 GM095583 (P.F.); by the Ministry of Science and Technology of China grant 2014CB910400 (Z.-j.L.); and by the NSF Science and Technology Center award 1231306 (J.C.H.S, U.W., W.L., and P.F.). C.G. thanks the PIER Helmholtz Graduate School and, together with L.G., A. Barty, and T.A.W., the Helmholtz Association for financial support through project-oriented funds. P.A.P. and V.C. acknowledge support from the Russian Ministry of Education and Science project 5-100. Parts of the sample delivery system used at LCLS for this research was funded by the NIH grant P41 GM103393, formerly P41 RR001209. Use of LCLS at Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under contract number DE-AC02-76SF00515. Publisher Copyright: 2016 {\textcopyright} The Authors.",
year = "2016",
month = sep,
doi = "10.1126/sciadv.1600292",
language = "English (US)",
volume = "2",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "9",
}