Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser
Yanyong Kang,X. Edward Zhou,Xiang Gao,Yuanzheng He,Wei Liu,Andrii Ishchenko,Anton Barty,Thomas A. White,Oleksandr Yefanov,Gye Won Han,Qingping Xu,Parker W. de Waal,Jiyuan Ke,M. H. Eileen Tan,Chenghai Zhang,Arne Moeller,Graham M. West,Bruce D. Pascal,Ned Van Eps,Lydia N. Caro,Sergey A. Vishnivetskiy,Regina J. Lee,Kelly Suino-Powell,Xin Gu,Kuntal Pal,Jinming Ma,Xiaoyong Zhi,Sébastien Boutet,Garth J. Williams,Marc Messerschmidt,Cornelius Gati,Nadia A. Zatsepin,Dingjie Wang,Daniel James,Shibom Basu,Shatabdi Roy-Chowdhury,Chelsie E. Conrad,Jesse Coe,Haiguang Liu,Stella Lisova,Christopher Kupitz,Ingo Grotjohann,Raimund Fromme,Yi Jiang,Minjia Tan,Huaiyu Yang,Jun Li,Meitian Wang,Zhong Zheng,Dianfan Li,Nicole Howe,Yingming Zhao,Jörg Standfuss,Kay Diederichs,Yuhui Dong,Clinton S. Potter,Bridget Carragher,Martin Caffrey,Hualiang Jiang,Henry N. Chapman,John C. H. Spence,Petra Fromme,Uwe Weierstall,Oliver P. Ernst,Vsevolod Katritch,Vsevolod V. Gurevich,Patrick R. Griffin,Wayne L. Hubbell,Raymond C. Stevens,Vadim Cherezov,Karsten Melcher,H. Eric Xu +71 more
TLDR
The crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin is determined by serial femtosecond X-ray laser crystallography and provides a basis for understanding GPCR-mediated arrestin-biased signalling.Abstract:
G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a similar to 20 degrees rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.read more
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DREADDs for Neuroscientists.
TL;DR: A primer on DREADDs is provided highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.
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GPCRDB: an information system for G protein-coupled receptors.
TL;DR: New features in the fifth major GPCRdb release are highlighted, including G PCR crystal structure browsing, superposition and display of ligand interactions, direct deposition by users of point mutations and their effects on ligand binding.
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The Molecular Basis of G Protein-Coupled Receptor Activation.
William I. Weis,Brian K. Kobilka +1 more
TL;DR: Molecular understanding of the allosteric coupling between ligand binding and G protein or arrestin interaction is emerging from structures of several GPCRs crystallized in inactive and active states, spectroscopic data, and computer simulations.
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Structure and dynamics of GPCR signaling complexes
TL;DR: Current insights into the structural plasticity of G PCR–G-protein and GPCR–arrestin complexes that underlies the regulation of the receptor’s intracellular signaling profile are summarized.
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GPCR Dynamics: Structures in Motion
TL;DR: What is currently known about the flexibility and dynamics of GPCRs, as determined through crystallography, spectroscopy, and computer simulations is reviewed.
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