@article{beb1281dbba7456294a002ceaabf8894,
title = "Atypical structural snapshots of human cytomegalovirus GPCR interactions with host G proteins",
abstract = "Human cytomegalovirus (HCMV) encodes G protein-coupled receptors (GPCRs) US28 and US27, which facilitate viral pathogenesis through engagement of host G proteins. Here we report cryo-electron microscopy structures of US28 and US27 forming nonproductive and productive complexes with Gi and Gq, respectively, exhibiting unusual features with functional implications. The “orphan” GPCR US27 lacks a ligand-binding pocket and has captured a guanosine diphosphate-bound inactive Gi through a tenuous interaction. The docking modes of CX3CL1-US28 and US27 to Gi favor localization to endosome-like curved membranes, where US28 and US27 can function as nonproductive Gi sinks to attenuate host chemokine-dependent Gi signaling. The CX3CL1-US28-Gq/11 complex likely represents a trapped intermediate during productive signaling, providing a view of a transition state in GPCR-G protein coupling for signaling. Our collective results shed new insight into unique G protein-mediated HCMV GPCR structural mechanisms, compared to mammalian GPCR counterparts, for subversion of host immunity.",
author = "Naotaka Tsutsumi and Shoji Maeda and Qianhui Qu and Martin V{\"o}gele and Jude, {Kevin M.} and Suomivuori, {Carl Mikael} and Ouliana Panova and Deepa Waghray and Kato, {Hideaki E.} and Andrew Velasco and Dror, {Ron O.} and Georgios Skiniotis and Kobilka, {Brian K.} and Garcia, {K. Christopher}",
note = "Funding Information: This work was supported by NIH funding R01AI125320 to K.C.G. and R01GM127359 to R.O.D. and a Stanford Bio-X seed grant to R.O.D. and G.S. K.C.G. is an investigator of the Howard Hughes Medical Institute and the Younger Family Chair and is supported by the Mathers Foundation. B.K.K. is a Chan Zuckerberg Biohub Investigator. N.T. (LT000011/2016-L) and C.-M.S. (LT000916/2018-L) were supported by Long-Term Fellowships from the Human Science Frontier Program Organization. M.V. was supported by an EMBO long-term fellowship (ALTF 235-2019). Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2022",
month = jan,
doi = "10.1126/sciadv.abl5442",
language = "English",
volume = "8",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "3",
}