Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis

Biochemistry. 2002 Mar 12;41(10):3321-8. doi: 10.1021/bi015905j.


Arrestin binding to activated, phosphorylated G protein-coupled receptors (GPCRs) represents a critical step in regulation of light- and hormone-dependent signaling. Nonvisual arrestins, such as arrestin-2, interact with multiple proteins for the purpose of propagating and terminating signaling events. Using a combination of X-ray crystallography, molecular modeling, mutagenesis, and binding analysis, we reveal structural features of arrestin-2 that may enable simultaneous binding to phosphorylated receptor, SH3 domains, phosphoinositides, and beta-adaptin. The structure of full-length arrestin-2 thus provides a uniquely oriented scaffold for assembly of multiple, diverse molecules involved in GPCR signal transduction.

Publication types

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

MeSH terms

  • Animals
  • Arrestins / chemistry
  • Arrestins / genetics
  • Arrestins / metabolism
  • Arrestins / physiology*
  • Cattle
  • Crystallography, X-Ray
  • Models, Molecular
  • Mutagenesis
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology*
  • Protein Binding
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Arrestins
  • Phosphoproteins
  • Recombinant Proteins

Associated data

  • PDB/1JSY