ArticleThe Journal of biological chemistry2019
Structural basis for the specificity of renin-mediated angiotensinogen cleavage.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Unraveling the molecular landscape and therapeutic strategies for acute kidney injury: insights from transcriptomics, network pharmacology, virtual screening, and in vitro experiments.Molecular diversity · 2026Article
- ProNotch converts extracellular protease activity into programmable transcriptional outputs.bioRxiv : the preprint server for biology · 2026Article
- Unveiling the Evolutionary History and Functional Significance of the Protein Z-Dependent Protease Inhibitor (ZPI) Across Vertebrates.Journal of molecular evolution · 2025Article
- The Molecular Pathology of Pre-Eclamptic Hypertension.Current issues in molecular biology · 2025Article
- Angiotensinogen and C3 compete for renin-induced complement activation.Frontiers in immunology · 2025Article
- Research Progress of Food-Derived Antihypertensive Peptides in Regulating the Key Factors of the Renin-Angiotensin System.Nutrients · 2024Review
- Review
- Renin and renin blockade have no role in complement activity.Kidney international · 2024Article
- Functional Exploration of Conserved Sequences in the Distal Face of Angiotensinogen-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Role of the Renin Angiotensin Aldosterone System in the Pathogenesis of Sepsis-Induced Acute Kidney Injury: A Systematic Review.Journal of clinical medicine · 2023Review
- Integrative modeling of diverse protein-peptide systems using CABS-dock.PLoS computational biology · 2023Article
- Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2.Frontiers in microbiology · 2023Review
- Immunoneutralization of human angiotensin-(1-12) with a monoclonal antibody in a humanized model of hypertension.Peptides · 2022Article
- View of the Renin-Angiotensin System in Acute Kidney Injury Induced by Renal Ischemia-Reperfusion Injury.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2022Review
- Hepcidin is potential regulator for renin activity.PloS one · 2022Article
- Angiotensinogen and the Modulation of Blood Pressure.Frontiers in cardiovascular medicine · 2021Review
- Article
- Investigation renin inhibitor activity from flavonoids derivates byJournal of advanced pharmaceutical technology & researchArticle
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
The renin-angiotensin cascade is a hormone system that regulates blood pressure and fluid balance. Renin-mediated cleavage of the angiotensin I peptide from the N terminus of angiotensinogen (AGT) is the rate-limiting step of this cascade; however, the detailed molecular mechanism underlying this step is unclear. Here, we solved the crystal structures of glycosylated human AGT (2.30 Å resolution), its encounter complex with renin (2.55 Å), AGT cleaved in its reactive center loop (RCL; 2.97 Å), and spent AGT from which the N-terminal angiotensin peptide was removed (2.63 Å). These structures revealed that AGT undergoes profound conformational changes and binds renin through a tail-into-mouth allosteric mechanism that inserts the N terminus into a pocket equivalent to a hormone-binding site on other serpins. These changes fully extended the N-terminal tail, with the scissile bond for angiotensin release docked in renin's active site. Insertion of the N terminus into this pocket accompanied a complete unwinding of helix H of AGT, which, in turn, formed key interactions with renin in the complementary binding interface. Mutagenesis and kinetic analyses confirmed that renin-mediated production of angiotensin I is controlled by interactions of amino acid residues and glycan components outside renin's active-site cleft. Our findings indicate that AGT adapts unique serpin features for hormone delivery and binds renin through concerted movements in the N-terminal tail and in its main body to modulate angiotensin release. These insights provide a structural basis for the development of agents that attenuate angiotensin release by targeting AGT's hormone binding pocket.
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Registered trials
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.