Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis.
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.
Milano
Shawn K
SK
Structural Biology and Bioinformatics Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Pace
Helen C
HC
Kim
You-Me
YM
Brenner
Charles
C
Benovic
Jeffrey L
JL
D000818:Animals; D019390:Arrestins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D016296:Mutagenesis; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D019390:Arrestins; D010750:Phosphoproteins; D011994:Recombinant Proteins