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 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

doi:10.1038/nature14656

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. CaroSergey 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

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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 language	English (US)
Pages (from-to)	561-567
Number of pages	7
Journal	Nature
Volume	523
Issue number	7562
DOIs	https://doi.org/10.1038/nature14656
State	Published - Jul 30 2015

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Kang, Y., Zhou, X. E., Gao, X., He, Y., Liu, W., Ishchenko, A., Barty, A., White, T. A., Yefanov, O., Han, G. W., Xu, Q., De Waal, P. W., Ke, J., Tan, M. H. E., Zhang, C., Moeller, A., West, G. M., Pascal, B. D., Van Eps, N., ... 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

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

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title = "Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser",

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.",

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

year = "2015",

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doi = "10.1038/nature14656",

language = "English (US)",

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T1 - Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

AU - Kang, Yanyong

AU - Zhou, X. Edward

AU - Gao, Xiang

AU - He, Yuanzheng

AU - Liu, Wei

AU - Ishchenko, Andrii

AU - Barty, Anton

AU - White, Thomas A.

AU - Yefanov, Oleksandr

AU - Han, Gye Won

AU - Xu, Qingping

AU - De Waal, Parker W.

AU - Ke, Jiyuan

AU - Tan, M. H Eileen

AU - Zhang, Chenghai

AU - Moeller, Arne

AU - West, Graham M.

AU - Pascal, Bruce D.

AU - Van Eps, Ned

AU - Caro, Lydia N.

AU - Vishnivetskiy, Sergey A.

AU - Lee, Regina J.

AU - Suino-Powell, Kelly M.

AU - Gu, Xin

AU - Pal, Kuntal

AU - Ma, Jinming

AU - Zhi, Xiaoyong

AU - Boutet, Sébastien

AU - Williams, Garth J.

AU - Messerschmidt, Marc

AU - Gati, Cornelius

AU - Zatsepin, Nadia

AU - Wang, Dingjie

AU - James, Daniel

AU - Basu, Shibom

AU - Roy-Chowdhury, Shatabdi

AU - Conrad, Chelsie E.

AU - Coe, Jesse

AU - Liu, Haiguang

AU - Lisova, Stella

AU - Kupitz, Christopher

AU - Grotjohann, Ingo

AU - Fromme, Raimund

AU - Jiang, Yi

AU - Tan, Minjia

AU - Yang, Huaiyu

AU - Li, Jun

AU - Wang, Meitian

AU - Zheng, Zhong

AU - Li, Dianfan

AU - Howe, Nicole

AU - Zhao, Yingming

AU - Standfuss, Jörg

AU - Diederichs, Kay

AU - Dong, Yuhui

AU - Potter, Clinton S.

AU - Carragher, Bridget

AU - Caffrey, Martin

AU - Jiang, Hualiang

AU - Chapman, Henry N.

AU - Spence, John

AU - Fromme, Petra

AU - Weierstall, Uwe

AU - Ernst, Oliver P.

AU - Katritch, Vsevolod

AU - Gurevich, Vsevolod V.

AU - Griffin, Patrick R.

AU - Hubbell, Wayne L.

AU - Stevens, Raymond C.

AU - Cherezov, Vadim

AU - Melcher, Karsten

AU - Xu, H. Eric

PY - 2015/7/30

Y1 - 2015/7/30

N2 - 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.

AB - 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.

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DO - 10.1038/nature14656

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VL - 523

SP - 561

EP - 567

JO - Nature

JF - Nature

IS - 7562

ER -

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

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