TY - JOUR
T1 - The 2.8 Å crystal structure of visual arrestin
T2 - A model for arrestin's regulation
AU - Hirsch, Joel A.
AU - Schubert, Carsten
AU - Gurevich, Vsevolod V.
AU - Sigler, Paul B.
N1 - Funding Information:
This paper is dedicated to the memory of our colleague and friend, Serge Pares, who helped initiate this project. He and his wife are deeply missed. We are indebted to members of the Sigler lab for their help in data collection (R. Albright, R. Gaudet, T. Kawashima, Y. Korkhin, G. Meinke, and F. Tsai). We thank the staffs of NSLS (Dr. L. Berman and Dr. M. Capel), MacCHESS, and APS-SBC (Dr. A. Joachimiak), Dr. W. Minor and Dr. Z. Otwinowski for a prerelease of HKL2000, Dr. G. Olack for mass spectrometry, Dr. E. de la Fortelle for advice on use of SHARP, and Dr. P. Adams for help with CNS. The work at Yale is supported in part from a grant to P. B. S. (GM22324) from the National Institutes of Health and in Sun City from a National Institutes of Health grant to V. V. G. (EY11500). J. A. H. is a National Eye Institute postdoctoral fellow, and C. S. is a Fellow of the Deutsche Forschungsgemeinschaft.
PY - 1999/4/16
Y1 - 1999/4/16
N2 - G protein-coupled signaling is utilized by a wide variety of eukaryotes for communicating information from the extracellular environment. Signal termination is achieved by the action of the arrestins, which bind to activated, phosphorylated G protein-coupled receptors. We describe here crystallographic studies of visual arrestin in its basal conformation. The salient features of the structure are a bipartite molecule with an unusual polar core. This core is stabilized in part by an extended carboxy-terminal tail that locks the molecule into an inactive state. In addition, arrestin is found to be a dimer of two asymmetric molecules, suggesting an intrinsic conformational plasticity. In conjunction with biochemical and mutagenesis data, we propose a molecular mechanism by which arrestin is activated for receptor binding.
AB - G protein-coupled signaling is utilized by a wide variety of eukaryotes for communicating information from the extracellular environment. Signal termination is achieved by the action of the arrestins, which bind to activated, phosphorylated G protein-coupled receptors. We describe here crystallographic studies of visual arrestin in its basal conformation. The salient features of the structure are a bipartite molecule with an unusual polar core. This core is stabilized in part by an extended carboxy-terminal tail that locks the molecule into an inactive state. In addition, arrestin is found to be a dimer of two asymmetric molecules, suggesting an intrinsic conformational plasticity. In conjunction with biochemical and mutagenesis data, we propose a molecular mechanism by which arrestin is activated for receptor binding.
UR - https://www.scopus.com/pages/publications/0033574274
U2 - 10.1016/S0092-8674(00)80735-7
DO - 10.1016/S0092-8674(00)80735-7
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AN - SCOPUS:0033574274
SN - 0092-8674
VL - 97
SP - 257
EP - 269
JO - Cell
JF - Cell
IS - 2
ER -