Molecular mechanism of phosphorylation-dependent arrestin activation.

Abstract:

:The past years have seen tremendous progress towards understanding how arrestins recognize phosphorylated G protein-coupled receptors (GPCRs). Two arrestin crystal structures, one of a pre-activated splice variant and one bound to a GPCR phosphopeptide, provided insights into the conformational changes upon phosphate recognition. Scanning mutagenesis and spectroscopic studies complete the picture of arrestin activation and receptor binding. Most perspicuous is the C-tail exchange mechanism, by which the C-tail of arrestin is released from its basal conformation and replaced by the phosphorylated GPCR C-terminus. Three positively charged clusters could act as conserved arrestin phosphosensors. Variations in the pattern of phosphorylation in a GPCR and variations within the C-terminus of different GPCRs may encode specificity to arrestin subtypes and particular physiological responses.

journal_name

Curr Opin Struct Biol

authors

Ostermaier MK,Schertler GF,Standfuss J

doi

10.1016/j.sbi.2014.07.006

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

143-51

eissn

0959-440X

issn

1879-033X

pii

S0959-440X(14)00078-5

journal_volume

29

pub_type

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