Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser Academic Article uri icon

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.

authors

  • 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, MH 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 CH
  • 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

publication date

  • 2015

published in