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Angiotensinogen and the Modulation of Blood Pressure
Zimei Shu1, Jiahui Wan1, Randy J Read2
1Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Frontiers in Cardiovascular Medicine
|April 5, 2021
Summary
Angiotensinogen
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Angiotensin peptides regulate blood pressure via angiotensinogen cleavage by renin.
- Angiotensinogen was previously considered a passive substrate.
- Understanding this interaction is key to blood pressure control.
Purpose of the Study:
- To elucidate the conformational mechanism of angiotensinogen cleavage by renin.
- To reveal the molecular details of angiotensin peptide release.
- To explore therapeutic strategies for hypertension.
Main Methods:
- X-ray crystallography of angiotensinogen and its complexes with renin.
- Analysis of angiotensinogen's N-terminal tail structure and dynamics.
- Investigation of disulfide bond influence on angiotensin release.
Main Results:
- Angiotensinogen possesses an inherent conformational mechanism for angiotensin release.
- Renin binding induces a significant shift in angiotensinogen's N-terminal tail.
- A labile disulfide bond and tail-in-mouth allosteric mechanism regulate cleavage.
- Species specificity and carbohydrate linkage effects were explained.
Conclusions:
- The conformational flexibility of angiotensinogen is crucial for blood pressure regulation.
- This mechanism offers insights into renin-angiotensin system dynamics.
- Novel hypertension treatments targeting this interaction are feasible.
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