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Trends Pharmacol Sci. 2013 Aug;34(8):470-8. doi: 10.1016/j.tips.2013.06.002. Epub 2013 Jul 11.

Matching structure with function: the GAIN domain of adhesion-GPCR and PKD1-like proteins.

Author information

1
Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.

Abstract

Elucidation of structural information can greatly facilitate the understanding of molecular function. A recent example is the description of the G-protein-coupled receptor (GPCR) autoproteolysis-inducing (GAIN) domain, an evolutionarily ancient fold present in Adhesion-GPCRs (aGPCRs) and polycystic kidney disease 1 (PKD1)-like proteins. In the past, the peculiar autoproteolytic capacity of both membrane protein families at the conserved GPCR proteolysis site (GPS) had not been described in detail. The physiological performance of aGPCRs and PKD1-like proteins is thought to be regulated through the GPS, but it is debated how. A recent report provides pivotal details by discovery and analysis of the GAIN domain structure that incorporates the GPS motif. Complementary studies have commenced to analyze physiological requirements of the GAIN domain for aGPCR function, indicating that it serves as the linchpin for multiple receptor signals. Structural analysis and functional assays now allow for the dissection of the biological duties conferred through the GAIN domain.

KEYWORDS:

GPCR proteolysis site (GPS); autocatalytic cleavage; disease-associated mutations; receptor activity

PMID:
23850273
DOI:
10.1016/j.tips.2013.06.002
[Indexed for MEDLINE]
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