| Structural highlights
Function
ANGT_MOUSE Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.[1] [2] Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone (By similarity).[3] [4] Angiotensin-3: stimulates aldosterone release (By similarity).[5] [6] Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1. Has vasodilator and antidiuretic effects. Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets.[7] [8]
Publication Abstract from PubMed
Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 A resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 A structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.
A redox switch in angiotensinogen modulates angiotensin release.,Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, Stein PE, Pipkin FB, Read RJ Nature. 2010 Oct 6. PMID:20927107[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63. Epub 2003 Jun 26. PMID:12829792 doi:http://dx.doi.org/10.1073/pnas.1432869100
- ↑ Fraga-Silva RA, Pinheiro SV, Goncalves AC, Alenina N, Bader M, Santos RA. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 2008 Jan-Feb;14(1-2):28-35. PMID:18026570 doi:http://dx.doi.org/10.2119/2007-00073.Fraga-Silva
- ↑ Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63. Epub 2003 Jun 26. PMID:12829792 doi:http://dx.doi.org/10.1073/pnas.1432869100
- ↑ Fraga-Silva RA, Pinheiro SV, Goncalves AC, Alenina N, Bader M, Santos RA. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 2008 Jan-Feb;14(1-2):28-35. PMID:18026570 doi:http://dx.doi.org/10.2119/2007-00073.Fraga-Silva
- ↑ Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63. Epub 2003 Jun 26. PMID:12829792 doi:http://dx.doi.org/10.1073/pnas.1432869100
- ↑ Fraga-Silva RA, Pinheiro SV, Goncalves AC, Alenina N, Bader M, Santos RA. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 2008 Jan-Feb;14(1-2):28-35. PMID:18026570 doi:http://dx.doi.org/10.2119/2007-00073.Fraga-Silva
- ↑ Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63. Epub 2003 Jun 26. PMID:12829792 doi:http://dx.doi.org/10.1073/pnas.1432869100
- ↑ Fraga-Silva RA, Pinheiro SV, Goncalves AC, Alenina N, Bader M, Santos RA. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 2008 Jan-Feb;14(1-2):28-35. PMID:18026570 doi:http://dx.doi.org/10.2119/2007-00073.Fraga-Silva
- ↑ Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, Stein PE, Pipkin FB, Read RJ. A redox switch in angiotensinogen modulates angiotensin release. Nature. 2010 Oct 6. PMID:20927107 doi:10.1038/nature09505
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