View source for 8el7


==CryoEM structure of Resistance to Inhibitors of Cholinesterase-8B (Ric-8B) in complex with G alpha s==
<StructureSection load='8el7' size='340' side='right'caption='[[8el7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8el7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EL7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=8el7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8el7 OCA], [https://pdbe.org/8el7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8el7 RCSB], [https://www.ebi.ac.uk/pdbsum/8el7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8el7 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN] Pseudopseudohypoparathyroidism;Pseudohypoparathyroidism type 1A;Progressive osseous heteroplasia;Polyostotic fibrous dysplasia;Monostotic fibrous dysplasia;Pseudohypoparathyroidism type 1C;Pseudohypoparathyroidism type 1B;McCune-Albright syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN] Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).<ref>PMID:12391161</ref> <ref>PMID:17110384</ref> <ref>PMID:21488135</ref> <ref>PMID:26206488</ref> <ref>PMID:8702665</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian Ric-8 proteins act as chaperones to regulate the cellular abundance of heterotrimeric G protein alpha subunits. The Ric-8A isoform chaperones Galphai/o, Galpha12/13, and Galphaq/11 subunits, while Ric-8B acts on Galphas/olf subunits. Here, we determined cryoelectron microscopy (cryo-EM) structures of Ric-8B in complex with Galphas and Galphaolf, revealing isoform differences in the relative positioning and contacts between the C-terminal alpha5 helix of Galpha within the concave pocket formed by Ric-8 alpha-helical repeat elements. Despite the overall architectural similarity with our earlier structures of Ric-8A complexed to Galphaq and Galphai1, Ric-8B distinctly accommodates an extended loop found only in Galphas/olf proteins. The structures, along with results from Ric-8 protein thermal stability assays and cell-based Galphaolf folding assays, support a requirement for the Galpha C-terminal region for binding specificity, and highlight that multiple structural elements impart specificity for Ric-8/G protein binding.

Structures of Ric-8B in complex with Galpha protein folding clients reveal isoform specificity mechanisms.,Papasergi-Scott MM, Kwarcinski FE, Yu M, Panova O, Ovrutsky AM, Skiniotis G, Tall GG Structure. 2023 May 4;31(5):553-564.e7. doi: 10.1016/j.str.2023.02.011. Epub 2023 , Mar 16. PMID:36931277<ref>PMID:36931277</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8el7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Papasergi-Scott MM]]
[[Category: Skiniotis G]]