Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

By Yanyong Kang, X. E. Zhou, Xiang Gao, Yuanzheng He, Wei Liu, A. Ishchenko, A. Barty, T. A. White, O. Yefanov, G. Han and 61 more. Nature, 2014

759 citations recorded by the source corpus.

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 ∼20° 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.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/0444dec7578a878d7e4fd79d0d1c706c953b5531

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Citations in the corpus

An Overview of the Top Ten Detergents Used for Membrane Protein Crystallization (2017, background): “It has been reported to be efficient both at protein extraction and stabilization of several delicate membrane proteins [37,61,62].”
Integrating structural and mutagenesis data to elucidate GPCR ligand binding (2016, background): “Another intriguing outlook is to extend the concept of data-driven mutation design to other functional sites, that is the binding sites of G proteins [48,49], b-arrestin [50], and dimerisation interfaces [51].”
The Molecular Basis of G Protein–Coupled Receptor Activation (2018, background): “Recently, the crystal structure of rhodopsin bound to visual arrestin was determined (70, 71).”
Advances in methods for atomic resolution macromolecular structure determination (2020, background): “Furthermore, because serial crystallography enables efficient measurements from small crystals, the technique has produced crystal structures of challenging targets for which large crystals could not be obtained, including proteins such as GPCR–arrestin complexes 180 and RNA polymerase 181 .”
GPCRdb: an information system for G protein-coupled receptors (2015, background): “These have revealed mechanisms of orthosteric and allosteric (9) ligand binding, conformational changes upon receptor activation (10–12), and the modes of binding of G protein (13,14) and -arrestin (15) signal mediators.”
GPCRdb: the G protein‐coupled receptor database – an introduction (2016, background): “However, structures of fully activated receptorsaresofarlimited to complexes of β 2 -adrenoceptor to Gs (Rasmussen et al., 2011), opsin (activated rhodopsin) to β -arrestin (Kang et al., 2015), or a G t α -subunit C-terminus (Scheerer et al., 2008), and the μ”
Serial Synchrotron X-Ray Crystallography (SSX). (2017, background): “The LCP injector reduces sample consumption dramatically (50- to 100-fold) compared to the GDVN injector and has enabled structure determination with SFX methods of several membrane proteins and complexes (β-adrenergic receptor [24], opioid receptor [25], angiotensin receptor [26], and rhodopsin-arr”
Pharmacogenomics of GPCR Drug Targets (2018, neutral): “These positions make extensive non-covalent contacts with G-protein and arrestin, respectively (Kang et al., 2015; Liang et al., 2017; Rasmussen et al., 2011; Zhang et al., 2017) and hence are important for intracellular signaling and drug response.”
An Online Resource for GPCR Structure Determination and Analysis (2019, background): “Moreover, for classes A and B1, structures of active states are also available, including complexes with an effector G protein 3–6 or β -arrestin 7 (for class A only).”