View source for 4dlq


==Crystal structure of the GAIN and HormR domains of CIRL 1/Latrophilin 1 (CL1)==
<StructureSection load='4dlq' size='340' side='right'caption='[[4dlq]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dlq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DLQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DLQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dlq OCA], [https://pdbe.org/4dlq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dlq RCSB], [https://www.ebi.ac.uk/pdbsum/4dlq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dlq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AGRL1_RAT 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.
<div style="background-color:#fffaf0;">
== 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<ref>PMID:22333914</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dlq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Latrophilin|Latrophilin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Arac D]]
[[Category: Bolliger MF]]
[[Category: Boucard AA]]
[[Category: Brunger AT]]
[[Category: Nguyen J]]
[[Category: Soltis M]]
[[Category: Sudhof TC]]