7ul5
From Proteopedia
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==CryoEM Structure of Inactive SSTR2 bound to Nb6== | ==CryoEM Structure of Inactive SSTR2 bound to Nb6== | ||
| - | <StructureSection load='7ul5' size='340' side='right'caption='[[7ul5]]' scene=''> | + | <StructureSection load='7ul5' size='340' side='right'caption='[[7ul5]], [[Resolution|resolution]] 3.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UL5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ul5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UL5 FirstGlance]. <br> |
| - | </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=7ul5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ul5 OCA], [https://pdbe.org/7ul5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ul5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ul5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ul5 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</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=7ul5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ul5 OCA], [https://pdbe.org/7ul5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ul5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ul5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ul5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/OPRK_HUMAN OPRK_HUMAN] G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.<ref>PMID:12004055</ref> <ref>PMID:22437504</ref> <ref>PMID:7624359</ref> <ref>PMID:8060324</ref> [https://www.uniprot.org/uniprot/SSR2_HUMAN SSR2_HUMAN] Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.<ref>PMID:15231824</ref> <ref>PMID:18653781</ref> <ref>PMID:19434240</ref> <ref>PMID:22495673</ref> <ref>PMID:22932785</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cryogenic electron microscopy (cryo-EM) has widened the field of structure-based drug discovery by allowing for routine determination of membrane protein structures previously intractable. Despite representing one of the largest classes of therapeutic targets, most inactive-state G protein-coupled receptors (GPCRs) have remained inaccessible for cryo-EM because their small size and membrane-embedded nature impedes projection alignment for high-resolution map reconstructions. Here we demonstrate that the same single-chain camelid antibody (nanobody) recognizing a grafted intracellular loop can be used to obtain cryo-EM structures of inactive-state GPCRs at resolutions comparable or better than those obtained by X-ray crystallography. Using this approach, we obtained structures of neurotensin 1 receptor bound to antagonist SR48692, mu-opioid receptor bound to alvimopan, apo somatostatin receptor 2 and histamine receptor 2 bound to famotidine. We expect this rapid, straightforward approach to facilitate the broad exploration of GPCR inactive states without the need for extensive engineering and crystallization. | ||
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| + | Structure determination of inactive-state GPCRs with a universal nanobody.,Robertson MJ, Papasergi-Scott MM, He F, Seven AB, Meyerowitz JG, Panova O, Peroto MC, Che T, Skiniotis G Nat Struct Mol Biol. 2022 Dec;29(12):1188-1195. doi: 10.1038/s41594-022-00859-8. , Epub 2022 Nov 17. PMID:36396979<ref>PMID:36396979</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ul5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Lama glama]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Robertson | + | [[Category: Robertson MJ]] |
| + | [[Category: Skiniotis G]] | ||
Current revision
CryoEM Structure of Inactive SSTR2 bound to Nb6
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