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Structural insights into ligand recognition and activation of angiotensin receptors.

ABSTRACT: G protein-coupled angiotensin II receptors, AT₁R and AT₂R, are integral components of the renin-angiotensin system (RAS) that regulates blood pressure and fluid balance in humans. While AT₁R is a well-established target of angiotensin receptor blockers (ARBs) for managing hypertension and a prime system for studying biased signaling, AT₂R has been recognized as a promising target against neuropathic pain and lung fibrosis. In this review, we discuss how recent structural advances illuminate ligand-binding modes and subtype selectivity, shared and distinct features of the receptors, their transducer-coupling patterns, and downstream signaling responses. We also underscore the key ATR aspects that require further studies to fully appreciate the mechanistic framework that fine-tunes their cellular and physiological functions, providing untapped potential for drug discovery.

SUBMITTER: Zhang H

PROVIDER: S-EPMC7611150 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Structural insights into ligand recognition and activation of angiotensin receptors.

Zhang Haitao H Luginina Aleksandra A Mishin Alexey A Baidya Mithu M Shukla Arun K AK Cherezov Vadim V

Trends in pharmacological sciences 20210510 7

G protein-coupled angiotensin II receptors, AT1R and AT2R, are integral components of the renin-angiotensin system (RAS) that regulates blood pressure and fluid balance in humans. While AT1R is a well-established target of angiotensin receptor blockers (ARBs) for managing hypertension and a prime system for studying biased signaling, AT2R has been recognized as a promising target against neuropathic pain and lung fibrosis. In this review, we discuss ho ...[more]

PMID: 33985815

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