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

Open access
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 A., 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 C. H., 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·2015·Nature

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 ∼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.

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Authors
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., Caro, L. N., Vishnivetskiy, S. A., Lee, R. J., Suino-Powell, K. M., Gu, X., Pal, K., Ma, J., Zhi, X., Boutet, S., Williams, G. J., Messerschmidt, M., Gati, C., Zatsepin, N. A., Wang, D., James, D., Basu, S., Roy-Chowdhury, S., Conrad, C. E., 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, C. S., Carragher, B., Caffrey, M., Jiang, H., Chapman, H. N., Spence, J. C. H., Fromme, P., Weierstall, U., Ernst, O. P., Katritch, V., Gurevich, V. V., Griffin, P. R., Hubbell, W. L., Stevens, R. C., Cherezov, V., Melcher, K., & Xu, H. E.
Venue
Nature
Published
2015-07-22
Volume
523
Issue
7562
Pages
561-567
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2165775221
Cited by
807
References
9
FWCI
44.90
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. https://app.cochat.ai/papers/10.1038/nature14656
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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. https://doi.org/10.1038/nature14656

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