4DLO

Crystal structure of the GAIN and HormR domains of brain angiogenesis inhibitor 3 (BAI3)

Summary for 4DLO

• Entry DOI: 10.2210/pdb4dlo/pdb
• Related: 4DLQ
• Descriptor: Brain-specific angiogenesis inhibitor 3, beta-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: gain domain, includes gps motif, autoproteolytic fold, extracellular, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Multi-pass membrane protein: O60242
• Total number of polymer chains: 2
• Total formula weight: 89126.00

Authors

Arac, D.,Boucard, A.A.,Bolliger, M.F.,Nguyen, J.,Soltis, M.,Sudhof, T.C.,Brunger, A.T. (deposition date: 2012-02-06, release date: 2012-02-22, Last modification date: 2024-10-16)

Primary citation

Arac, D.,Boucard, A.A.,Bolliger, M.F.,Nguyen, J.,Soltis, S.M.,Sudhof, T.C.,Brunger, A.T.
A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis.
Embo J., 31:1364-1378, 2012

PubMed Abstract: The G protein-coupled receptor (GPCR) Proteolysis Site (GPS) of cell-adhesion GPCRs and polycystic kidney disease (PKD) proteins constitutes a highly conserved autoproteolysis sequence, but its catalytic mechanism remains unknown. Here, we show that unexpectedly the ∼40-residue GPS motif represents an integral part of a much larger ∼320-residue domain that we termed GPCR-Autoproteolysis INducing (GAIN) domain. Crystal structures of GAIN domains from two distantly related cell-adhesion GPCRs revealed a conserved novel fold in which the GPS motif forms five β-strands that are tightly integrated into the overall GAIN domain. The GAIN domain is evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. Functionally, the GAIN domain is both necessary and sufficient for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyse peptide bond hydrolysis. Thus, the GAIN domain embodies a unique, evolutionarily ancient and widespread autoproteolytic fold whose function is likely relevant for GPCR signalling and for multiple human diseases.

PubMed: 22333914
DOI: 10.1038/emboj.2012.26

Experimental method

X-RAY DIFFRACTION (2.3 Å)