7xt9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:42, 9 October 2024) (edit) (undo)
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7xt9]] is a 4 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=7XT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XT9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7xt9]] is a 4 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=7XT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XT9 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=SRO:SEROTONIN'>SRO</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]] 3.2&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=SRO:SEROTONIN'>SRO</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=7xt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xt9 OCA], [https://pdbe.org/7xt9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xt9 RCSB], [https://www.ebi.ac.uk/pdbsum/7xt9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xt9 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=7xt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xt9 OCA], [https://pdbe.org/7xt9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xt9 RCSB], [https://www.ebi.ac.uk/pdbsum/7xt9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xt9 ProSAT]</span></td></tr>
</table>
</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 ==
== 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>
+
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/5HT4R_HUMAN 5HT4R_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:10821780, PubMed:16102731, PubMed:35714614, PubMed:9603189). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:16102731, PubMed:35714614). HTR4 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:16102731, PubMed:35714614).<ref>PMID:10821780</ref> <ref>PMID:16102731</ref> <ref>PMID:35714614</ref> <ref>PMID:9603189</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
-
Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of Gs, Gi, or Gq proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT4, 5-HT6, and 5-HT7 with Gs, and 5-HT4 with Gi1. The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for Gs and Gi, respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with Gs or Gi. Together, these results present a common mechanism of Gs versus Gi protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors.
+
Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of G(s), G(i,) or G(q) proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT(4), 5-HT(6), and 5-HT(7) with G(s), and 5-HT(4) with G(i1). The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for G(s) and G(i), respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with G(s) or G(i). Together, these results present a common mechanism of G(s) versus G(i) protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors.
-
GPCRs steer Gi and Gs selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors.,Huang S, Xu P, Shen DD, Simon IA, Mao C, Tan Y, Zhang H, Harpsoe K, Li H, Zhang Y, You C, Yu X, Jiang Y, Zhang Y, Gloriam DE, Xu HE Mol Cell. 2022 Jul 21;82(14):2681-2695.e6. doi: 10.1016/j.molcel.2022.05.031., Epub 2022 Jun 16. PMID:35714614<ref>PMID:35714614</ref>
+
GPCRs steer G(i) and G(s) selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors.,Huang S, Xu P, Shen DD, Simon IA, Mao C, Tan Y, Zhang H, Harpsoe K, Li H, Zhang Y, You C, Yu X, Jiang Y, Zhang Y, Gloriam DE, Xu HE Mol Cell. 2022 Jul 21;82(14):2681-2695.e6. doi: 10.1016/j.molcel.2022.05.031. , Epub 2022 Jun 16. PMID:35714614<ref>PMID:35714614</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>
Line 22: Line 21:
==See Also==
==See Also==
 +
*[[Transducin 3D structures|Transducin 3D structures]]
*[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]]
*[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]]
== References ==
== References ==

Current revision

Serotonin 4 (5-HT4) receptor-Gs complex

PDB ID 7xt9

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7xt9"
Personal tools