4DLQ
Crystal structure of the GAIN and HormR domains of CIRL 1/Latrophilin 1 (CL1)
Summary for 4DLQ
| Entry DOI | 10.2210/pdb4dlq/pdb |
| Related | 4DLO |
| Descriptor | Latrophilin-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | gain domain, includes the gps motif, hormone binding domain, autoproteolysis, a-latrotoxin, extracellular domain, signaling protein |
| Biological source | Rattus norvegicus (rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 46466.97 |
| 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: 2024-10-09) |
| 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 Cited by 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: 22333914DOI: 10.1038/emboj.2012.26 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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