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

• Autores: Yanyong Kang, Edward X. Zhou, Xiang Gao, Yuanzheng He, Wei Liu, Andrii Ishchenko, Anton Barty, Thomas A. White
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 523, Nº 7562, 2015, págs. 561-567
• Idioma: inglés
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• Resumen

  • 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.