3p2d

Publication Abstract from PubMed

Arrestins are multi-functional proteins that regulate signaling and trafficking of the majority of G protein-coupled receptors (GPCRs), as well as sub-cellular localization and activity of many other signaling proteins. We report the first crystal structure of arrestin-3, solved at 3.0 A resolution. Arrestin-3 is an elongated two-domain molecule with overall fold and key inter-domain interactions that hold free protein in the basal conformation similar to the other subtypes. Arrestin-3 is the least selective member of the family, binding a wide variety of GPCRs with high affinity and demonstrating lower preference for active phosphorylated forms of the receptors. In contrast to the other three arrestins, part of the receptor-binding surface in the arrestin-3 C-domain does not form a contiguous beta-sheet, which is consistent with increased flexibility. By swapping the corresponding elements between arrestin-2 and arrestin-3 we show that the presence of this loose structure is correlated with reduced arrestin selectivity for activated receptor, consistent with a conformational change in this beta-sheet upon receptor binding.

Crystal Structure of Arrestin-3 Reveals the Basis of the Difference in Receptor Binding Between Two Non-visual Subtypes.,Zhan X, Gimenez LE, Gurevich VV, Spiller BW J Mol Biol. 2011 Jan 6. PMID:21215759^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.