ArticleNature communications2023
Membrane mediated mechanical stimuli produces distinct active-like states in the AT1 receptor.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 18 citations in OpenAlex.
- All-Atom Simulations Reveal the Effect of Membrane Composition on the Signaling of the NKG2A/CD94/HLA-E Immune Receptor Complex.Journal of chemical information and modeling · 2024Article
- Mechanical induction in metazoan development and evolution: from earliest multi-cellular organisms to modern animal embryos.Nature communications · 2024Review
- Role of local angiotensin II signaling in bladder function.American journal of physiology. Renal physiology · 2024Review
- Mechanical stress and anionic lipids synergistically stabilize an atypical structure of the angiotensin II type 1 receptor (AT1).PLoS computational biology · 2024Article
- Precise control of transmembrane current via regulating bionic lipid membrane composition.Science advances · 2024Article
- A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Membrane mediated mechanical stimuli produces distinct active-like states in the AT1 receptor.Nature communications · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Angiotensin II Type 1 (AT1) receptor is one of the most widely studied GPCRs within the context of biased signaling. While the AT1 receptor is activated by agonists such as the peptide AngII, it can also be activated by mechanical stimuli such as membrane stretch or shear in the absence of a ligand. Despite the importance of mechanical activation of the AT1 receptor in biological processes such as vasoconstriction, little is known about the structural changes induced by external physical stimuli mediated by the surrounding lipid membrane. Here, we present a systematic simulation study that characterizes the activation of the AT1 receptor under various membrane environments and mechanical stimuli. We show that stability of the active state is highly sensitive to membrane thickness and tension. Structural comparison of membrane-mediated vs. agonist-induced activation shows that the AT1 receptor has distinct active conformations. This is supported by multi-microsecond free energy calculations that show unique landscapes for the inactive and various active states. Our modeling results provide structural insights into the mechanical activation of the AT1 receptor and how it may produce different functional outcomes within the framework of biased agonism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.