View source for 7xms


==CryoEM structure of somatostatin receptor 4 (SSTR4) in complex with Gi1 and its endogeneous ligand SST-14==
<StructureSection load='7xms' size='340' side='right'caption='[[7xms]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xms]] is a 6 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=7XMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XMS 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]] 2.9&#8491;</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=7xms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xms OCA], [https://pdbe.org/7xms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xms RCSB], [https://www.ebi.ac.uk/pdbsum/7xms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xms ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SSR4_HUMAN SSR4_HUMAN] Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of G(i1)-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of G(i1)-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs.

Structural insights into ligand recognition and selectivity of somatostatin receptors.,Zhao W, Han S, Qiu N, Feng W, Lu M, Zhang W, Wang M, Zhou Q, Chen S, Xu W, Du J, Chu X, Yi C, Dai A, Hu L, Shen MY, Sun Y, Zhang Q, Ma Y, Zhong W, Yang D, Wang MW, Wu B, Zhao Q Cell Res. 2022 Aug;32(8):761-772. doi: 10.1038/s41422-022-00679-x. Epub 2022 Jun , 23. PMID:35739238<ref>PMID:35739238</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xms" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Dehua Y]]
[[Category: Mengjie L]]
[[Category: Ming-Wei W]]
[[Category: Na Q]]
[[Category: Shuo H]]
[[Category: Wenbo Z]]
[[Category: Wenli Z]]
[[Category: Wu B]]
[[Category: Zhao Q]]