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Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
A redox switch in angiotensinogen modulates angiotensin release
Aiwu Zhou1, Robin W Carrell, Michael P Murphy
1Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. awz20@cam.ac.uk
Nature
|October 8, 2010
Summary
Blood pressure regulation involves angiotensinogen, a protein whose structure changes. This redox-responsive transition to a more active form may contribute to blood pressure modulation, particularly in pre-eclampsia.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Blood pressure is regulated by angiotensins, derived from angiotensinogen.
- Angiotensinogen was previously considered a passive substrate for renin.
- The enzyme renin cleaves angiotensinogen to release vasopressor peptides.
Purpose of the Study:
- To elucidate the structural basis of angiotensinogen activation by renin.
- To investigate the role of angiotensinogen conformation in blood pressure control.
- To explore the redox-dependent regulation of angiotensinogen activity.
Main Methods:
- X-ray crystallography to determine the structures of human angiotensinogen and its complex with renin.
- Analysis of the conformational changes affecting the angiotensin cleavage site.
- Assessment of the redox state of angiotensinogen in circulation.
Main Results:
- The angiotensin cleavage site in angiotensinogen is buried in its native state.
- A conserved disulfide bridge links conformational changes that expose the cleavage site.
- Angiotensinogen exists in two redox states in circulation, with the oxidized form preferentially binding renin.
- An oxidative switch to the active, bridged form is observed in pre-eclampsia.
Conclusions:
- A redox-responsive conformational transition of angiotensinogen regulates angiotensin release.
- This mechanism contributes to blood pressure modulation.
- The oxidative switch is implicated in the hypertensive crisis of pre-eclampsia.
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