Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation

Structure. 2001 Sep;9(9):869-80. doi: 10.1016/s0969-2126(01)00644-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arrestins / chemistry*
  • Arrestins / genetics
  • Arrestins / metabolism*
  • Binding Sites
  • Biological Transport
  • Cattle
  • Cell Membrane / metabolism*
  • Crystallography, X-Ray
  • Dimerization
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Models, Biological*
  • Models, Molecular
  • Molecular Sequence Data
  • Point Mutation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / metabolism*
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • beta-Arrestins


  • Arrestins
  • Receptors, Cell Surface
  • beta-Arrestins
  • Heterotrimeric GTP-Binding Proteins

Associated data

  • PDB/1G4M
  • PDB/1G4R