4dlq

Crystal structure of the GAIN and HormR domains of CIRL 1/Latrophilin 1 (CL1)Crystal structure of the GAIN and HormR domains of CIRL 1/Latrophilin 1 (CL1)

Structural highlights 4dlq is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AGRL1_RAT Calcium-independent receptor of high affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis. Isoform 2: Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization. Publication Abstract from PubMed 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 approximately 40-residue GPS motif represents an integral part of a much larger approximately 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 beta-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. A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis.,Arac D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Sudhof TC, Brunger AT EMBO J. 2012 Feb 14;31(6):1364-78. doi: 10.1038/emboj.2012.26. PMID:22333914 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Latrophilin

spinqualitylabelsall models 4dlq, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image