9uwl: Difference between revisions
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==Cryo-EM structure of human V1aR bound with SRX246 at a resolution of 2.6 angstrom== | |||
<StructureSection load='9uwl' size='340' side='right'caption='[[9uwl]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9uwl]] is a 2 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=9UWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9UWL 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]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EQN:(2~{R})-4-oxidanylidene-2-[(3~{S},4~{R})-2-oxidanylidene-3-[(4~{S})-2-oxidanylidene-4-phenyl-1,3-oxazolidin-3-yl]-4-[(~{E})-2-phenylethenyl]azetidin-1-yl]-~{N}-[(1~{R})-1-phenylethyl]-4-(4-piperidin-1-ylpiperidin-1-yl)butanamide'>A1EQN</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=9uwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9uwl OCA], [https://pdbe.org/9uwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9uwl RCSB], [https://www.ebi.ac.uk/pdbsum/9uwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9uwl ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Arginine vasopressin (AVP) and oxytocin (OT) are peptide hormones critical for various physiological processes. Vasopressin receptor 1 A (V1aR), a primary AVP target, is promising for central nervous system (CNS) disorders therapies, yet the mechanisms of antagonism and oligomerization remain poorly understood. Here, we present structures of human V1aR in its apo state and in complexes with antagonists: atosiban, balovaptan, and SRX246. Structural analyses reveal a dimeric V1aR assembly, validated by functional assays and imaging in cells. The apo structure shows a flat extracellular loop 2 (ECL2) with unpaired cysteines, undergoing significant conformational changes upon ligand binding. Antagonist-bound structures, combined with mutagenesis and radioligand binding assays, uncover distinct binding modes and key determinants for antagonism and selectivity. These findings provide a comprehensive understanding of V1aR assembly and dynamic regulation, offering valuable insights for structure-guided development of new antagonists targeting dimeric V1aR for CNS disorders. | |||
Molecular basis of antagonism of the dimeric human arginine vasopressin receptor 1A.,Zhong P, Chu B, Yu Z, Qiao Y, Ding Y, Zhang Y, Wu X Nat Commun. 2026 Jan 16. doi: 10.1038/s41467-026-68331-5. PMID:41545407<ref>PMID:41545407</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9uwl" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chu BX]] | |||
[[Category: Wu XW]] | |||
[[Category: Zhong PY]] | |||
Latest revision as of 19:32, 10 February 2026
Cryo-EM structure of human V1aR bound with SRX246 at a resolution of 2.6 angstrom
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