title: Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation.
abstract: BACKGROUND
  Arrestins are responsible for the desensitization of many sequence-divergent G protein-coupled receptors. They compete with G proteins for binding to activated phosphorylated receptors, initiate receptor internalization, and activate additional signaling pathways.
  
  
  RESULTS
  In order to understand the structural basis for receptor binding and arrestin's function as an adaptor molecule, we determined the X-ray crystal structure of two truncated forms of bovine beta-arrestin in its cytosolic inactive state to 1.9 A. Mutational analysis and chimera studies identify the regions in beta-arrestin responsible for receptor binding specificity. beta-arrestin demonstrates high structural homology with the previously solved visual arrestin. All key structural elements responsible for arrestin's mechanism of activation are conserved.
  
  
  CONCLUSIONS
  Based on structural analysis and mutagenesis data, we propose a previously unappreciated part in beta-arrestin's mode of action by which a cationic amphipathic helix may function as a reversible membrane anchor. This novel activation mechanism would facilitate the formation of a high-affinity complex between beta-arrestin and an activated receptor regardless of its specific subtype. Like the interaction between beta-arrestin's polar core and the phosphorylated receptor, such a general activation mechanism would contribute to beta-arrestin's versatility as a regulator of many receptors.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. mhan@mpi.com
authors.forename: M
authors.initials: M
authors.lastname: Han
authors.forename: V V
authors.initials: VV
authors.lastname: Gurevich
authors.forename: S A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: P B
authors.initials: PB
authors.lastname: Sigler
authors.forename: C
authors.initials: C
authors.lastname: Schubert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D011956:Receptors, Cell Surface; D000071557:beta-Arrestins; D020962:Heterotrimeric GTP-Binding Proteins