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 & 52 others Sergey A. Vishnivetskiy, Regina J. Lee, Kelly M. Suino-Powell, Xin Gu, Kuntal Pal, Jinming Ma, Xiaoyong Zhi, Sébastien Boutet, Garth J. Williams, Marc Messerschmidt, Cornelius Gati, Nadia 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 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

Research output: Contribution to journalArticle

336 Citations (Scopus)

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 ∼1/420° 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.

Original languageEnglish (US)
Pages (from-to)561-567
Number of pages7
JournalNature
Volume523
Issue number7562
DOIs
StatePublished - Jul 30 2015

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Arrestin
Rhodopsin
Lasers
X-Rays
G-Protein-Coupled Receptors
GTP-Binding Proteins
Arrestins
X Ray Crystallography
Mutagenesis

ASJC Scopus subject areas

  • General

Cite this

Kang, Y., Zhou, X. E., Gao, X., He, Y., Liu, W., Ishchenko, A., ... Xu, H. E. (2015). Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature, 523(7562), 561-567. https://doi.org/10.1038/nature14656

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. / Kang, Yanyong; Zhou, X. Edward; Gao, Xiang; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; Barty, Anton; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; De Waal, Parker W.; Ke, Jiyuan; Tan, M. H Eileen; Zhang, Chenghai; Moeller, Arne; West, Graham M.; Pascal, Bruce D.; Van Eps, Ned; Caro, Lydia N.; Vishnivetskiy, Sergey A.; Lee, Regina J.; Suino-Powell, Kelly M.; Gu, Xin; Pal, Kuntal; Ma, Jinming; Zhi, Xiaoyong; Boutet, Sébastien; Williams, Garth J.; Messerschmidt, Marc; Gati, Cornelius; Zatsepin, Nadia; Wang, Dingjie; James, Daniel; Basu, Shibom; Roy-Chowdhury, Shatabdi; Conrad, Chelsie E.; Coe, Jesse; Liu, Haiguang; Lisova, Stella; Kupitz, Christopher; Grotjohann, Ingo; Fromme, Raimund; Jiang, Yi; Tan, Minjia; Yang, Huaiyu; Li, Jun; Wang, Meitian; Zheng, Zhong; Li, Dianfan; Howe, Nicole; Zhao, Yingming; Standfuss, Jörg; Diederichs, Kay; Dong, Yuhui; Potter, Clinton S.; Carragher, Bridget; Caffrey, Martin; Jiang, Hualiang; Chapman, Henry N.; Spence, John; Fromme, Petra; Weierstall, Uwe; Ernst, Oliver P.; Katritch, Vsevolod; Gurevich, Vsevolod V.; Griffin, Patrick R.; Hubbell, Wayne L.; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric.

In: Nature, Vol. 523, No. 7562, 30.07.2015, p. 561-567.

Research output: Contribution to journalArticle

Kang, Y, Zhou, XE, Gao, X, He, Y, Liu, W, Ishchenko, A, Barty, A, White, TA, Yefanov, O, Han, GW, Xu, Q, De Waal, PW, Ke, J, Tan, MHE, Zhang, C, Moeller, A, West, GM, Pascal, BD, Van Eps, N, Caro, LN, Vishnivetskiy, SA, Lee, RJ, Suino-Powell, KM, Gu, X, Pal, K, Ma, J, Zhi, X, Boutet, S, Williams, GJ, Messerschmidt, M, Gati, C, Zatsepin, N, Wang, D, James, D, Basu, S, Roy-Chowdhury, S, Conrad, CE, Coe, J, Liu, H, Lisova, S, Kupitz, C, Grotjohann, I, Fromme, R, Jiang, Y, Tan, M, Yang, H, Li, J, Wang, M, Zheng, Z, Li, D, Howe, N, Zhao, Y, Standfuss, J, Diederichs, K, Dong, Y, Potter, CS, Carragher, B, Caffrey, M, Jiang, H, Chapman, HN, Spence, J, Fromme, P, Weierstall, U, Ernst, OP, Katritch, V, Gurevich, VV, Griffin, PR, Hubbell, WL, Stevens, RC, Cherezov, V, Melcher, K & Xu, HE 2015, 'Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser' Nature, vol. 523, no. 7562, pp. 561-567. https://doi.org/10.1038/nature14656
Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A et al. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-567. https://doi.org/10.1038/nature14656
Kang, Yanyong ; Zhou, X. Edward ; Gao, Xiang ; He, Yuanzheng ; Liu, Wei ; Ishchenko, Andrii ; Barty, Anton ; White, Thomas A. ; Yefanov, Oleksandr ; Han, Gye Won ; Xu, Qingping ; De Waal, Parker W. ; Ke, Jiyuan ; Tan, M. H Eileen ; Zhang, Chenghai ; Moeller, Arne ; West, Graham M. ; Pascal, Bruce D. ; Van Eps, Ned ; Caro, Lydia N. ; Vishnivetskiy, Sergey A. ; Lee, Regina J. ; Suino-Powell, Kelly M. ; Gu, Xin ; Pal, Kuntal ; Ma, Jinming ; Zhi, Xiaoyong ; Boutet, Sébastien ; Williams, Garth J. ; Messerschmidt, Marc ; Gati, Cornelius ; Zatsepin, Nadia ; Wang, Dingjie ; James, Daniel ; Basu, Shibom ; Roy-Chowdhury, Shatabdi ; Conrad, Chelsie E. ; Coe, Jesse ; Liu, Haiguang ; Lisova, Stella ; Kupitz, Christopher ; Grotjohann, Ingo ; Fromme, Raimund ; Jiang, Yi ; Tan, Minjia ; Yang, Huaiyu ; Li, Jun ; Wang, Meitian ; Zheng, Zhong ; Li, Dianfan ; Howe, Nicole ; Zhao, Yingming ; Standfuss, Jörg ; Diederichs, Kay ; Dong, Yuhui ; Potter, Clinton S. ; Carragher, Bridget ; Caffrey, Martin ; Jiang, Hualiang ; Chapman, Henry N. ; Spence, John ; Fromme, Petra ; Weierstall, Uwe ; Ernst, Oliver P. ; Katritch, Vsevolod ; Gurevich, Vsevolod V. ; Griffin, Patrick R. ; Hubbell, Wayne L. ; Stevens, Raymond C. ; Cherezov, Vadim ; Melcher, Karsten ; Xu, H. Eric. / Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. In: Nature. 2015 ; Vol. 523, No. 7562. pp. 561-567.
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