The 2.8 A crystal structure of visual arrestin: a model for arrestin's regulation.
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.
Hirsch
J A
JA
Howard Hughes Medical Institute, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511, USA.
Schubert
C
C
Gurevich
V V
VV
Sigler
P B
PB
D000595:Amino Acid Sequence; D000818:Animals; D019393:Arrestin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D019393:Arrestin; D011994:Recombinant Proteins