7y26: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7y26]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y26 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7y26]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y26 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene></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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</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=7y26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y26 OCA], [https://pdbe.org/7y26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y26 RCSB], [https://www.ebi.ac.uk/pdbsum/7y26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y26 ProSAT]</span></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=7y26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y26 OCA], [https://pdbe.org/7y26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y26 RCSB], [https://www.ebi.ac.uk/pdbsum/7y26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y26 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
G protein-coupled receptors (GPCRs) modulate every aspect of physiological functions mainly through activating heterotrimeric G proteins. A majority of GPCRs promiscuously couple to multiple G protein subtypes. Here we validate that in addition to the well-known Gi/o pathway, somatostatin receptor 2 and 5 (SSTR2 and SSTR5) couple to the Gq/11 pathway and show that smaller ligands preferentially activate the Gi/o pathway. We further determined cryo-electron microscopy structures of the SSTR2Go and SSTR2Gq complexes bound to octreotide and SST-14. Structural and functional analysis revealed that G protein selectivity of SSTRs is not only determined by structural elements in the receptor-G protein interface, but also by the conformation of the agonist-binding pocket. Accordingly, smaller ligands fail to stabilize a broader agonist-binding pocket of SSTRs that is required for efficient Gq/11 coupling but not Gi/o coupling. Our studies facilitate the design of drugs with selective G protein signaling to improve therapeutic efficacy.
G protein-coupled receptors (GPCRs) modulate every aspect of physiological functions mainly through activating heterotrimeric G proteins. A majority of GPCRs promiscuously couple to multiple G protein subtypes. Here we validate that in addition to the well-known G(i/o) pathway, somatostatin receptor 2 and 5 (SSTR2 and SSTR5) couple to the G(q/11) pathway and show that smaller ligands preferentially activate the G(i/o) pathway. We further determined cryo-electron microscopy structures of the SSTR2‒G(o) and SSTR2‒G(q) complexes bound to octreotide and SST-14. Structural and functional analysis revealed that G protein selectivity of SSTRs is not only determined by structural elements in the receptor-G protein interface, but also by the conformation of the agonist-binding pocket. Accordingly, smaller ligands fail to stabilize a broader agonist-binding pocket of SSTRs that is required for efficient G(q/11) coupling but not G(i/o) coupling. Our studies facilitate the design of drugs with selective G protein signaling to improve therapeutic efficacy.


Molecular basis for the selective G protein signaling of somatostatin receptors.,Chen S, Teng X, Zheng S Nat Chem Biol. 2022 Sep 22. pii: 10.1038/s41589-022-01130-3. doi:, 10.1038/s41589-022-01130-3. PMID:36138141<ref>PMID:36138141</ref>
Molecular basis for the selective G protein signaling of somatostatin receptors.,Chen S, Teng X, Zheng S Nat Chem Biol. 2023 Feb;19(2):133-140. doi: 10.1038/s41589-022-01130-3. Epub 2022 , Sep 22. PMID:36138141<ref>PMID:36138141</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 7y26" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 7y26" style="background-color:#fffaf0;"></div>
==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
== References ==
<references/>
<references/>
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