9UWL

Cryo-EM structure of human V1aR bound with SRX246 at a resolution of 2.6 angstrom

これはPDB形式変換不可エントリーです。

9UWL の概要

• エントリーDOI: 10.2210/pdb9uwl/pdb
• EMDBエントリー: 64559
• 分子名称: Vasopressin V1a receptor, SRX246, CHOLESTEROL, ... (4 entities in total)
• 機能のキーワード: gpcr, small molecule, antagonist, nanobody, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 90344.53

構造登録者

Wu, X.W.,Zhong, P.Y.,Chu, B.X. (登録日: 2025-05-12, 公開日: 2026-02-04, 最終更新日: 2026-02-25)

主引用文献

Zhong, P.,Chu, B.,Yu, Z.,Qiao, Y.,Ding, Y.,Zhang, Y.,Wu, X.
Molecular basis of antagonism of the dimeric human arginine vasopressin receptor 1A.
Nat Commun, 17:1622-1622, 2026

PubMed Abstract: 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.

PubMed: 41545407
DOI: 10.1038/s41467-026-68331-5

実験手法

ELECTRON MICROSCOPY (2.6 Å)