2X0B

Crystal structure of human angiotensinogen complexed with renin

Summary for 2X0B

• Entry DOI: 10.2210/pdb2x0b/pdb
• Related: 2WXW 2WXX 2WXY 2WXZ 2WY0 2WY1
• Descriptor: RENIN, ANGIOTENSINOGEN (2 entities in total)
• Functional Keywords: hydrolase-hormone complex, hydrolase hormone complex, vasoconstrictor, glycoprotein, hypertension, serpins, zymogen, hydrolase, vasoactive, hydrolase/hormone
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P00797 P01019
• Total number of polymer chains: 8
• Total formula weight: 368687.46

Authors

Zhou, A.,Wei, Z.,Yan, Y.,Carrell, R.W.,Read, R.J. (deposition date: 2009-12-08, release date: 2010-10-20, Last modification date: 2024-10-09)

Primary citation

Zhou, A.,Carrell, R.W.,Murphy, M.P.,Wei, Z.,Yan, Y.,Stanley, P.L.,Stein, P.E.,Pipkin, F.B.,Read, R.J.
A Redox Switch in Angiotensinogen Modulates Angiotensin Release.
Nature, 468:108-, 2010

PubMed Abstract: 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 Å 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 Å 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.

PubMed: 20927107
DOI: 10.1038/NATURE09505

Experimental method

X-RAY DIFFRACTION (4.33 Å)