The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone
The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone
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DOI：
10.1016/j.str.2019.12.003
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发表时间：
2020-04-07
期刊：
影响因子：
5.7
通讯作者：
Iwata, So
中科院分区：
文献类型：
--
作者：
Asada, Hidetsugu;Inoue, Asuka;Iwata, So
血管紧张素II （AngII）是一种肽激素，在调节血压中起关键作用，其与G蛋白偶联受体AngII -1型受体（AT(1)R）和AngII -2型受体（AT(2)R）的相互作用是其作用机制的核心。我们在3.2埃分辨率下解析了人AT(2)R与AngII结合的晶体结构及其特异性抗体。AngII（完全激动剂）和[Sar(1), Ile(8)]-AngII（部分激动剂）以类似的方式与AT(2)R相互作用，除了在AT(2)R配体结合袋的底部。特别是，Met128（3.36）等残基构成腔的深端，在AngII结合血管紧张素受体（angiotensin receptor， ATR）激活中发挥重要作用。内源性配体结合时发生的这些差异可能导致AT(2)R的结构变化，导致螺旋8的非规范配位正常化。我们的研究结果将为设计更有效的atr配体提供信息。
Angiotensin II (AngII) is a peptide hormone that plays a key role in regulating blood pressure, and its interactions with the G protein-coupled receptors, AngII type-1 receptor (AT(1)R) and AngII type-2 receptor (AT(2)R), are central to its mechanism of action. We solved the crystal structure of human AT(2)R bound to AngII and its specific antibody at 3.2-angstrom resolution. AngII (full agonist) and [Sar(1), Ile(8)]-AngII (partial agonist) interact with AT(2)R in a similar fashion, except at the bottom of the AT(2)R ligand-binding pocket. In particular, the residues including Met128(3.36), which constitute the deep end of the cavity, play important roles in angiotensin receptor (ATR) activation upon AngII binding. These differences that occur upon endogenous ligand binding may contribute to a structural change in AT(2)R, leading to normalization of the non-canonical coordination of helix 8. Our results will inform the design of more effective ligands for ATRs.