crystals of angiotensinogen and the complex of human angiotensinogen with de - glycosylated renin - asp292ala were grown at room temperature under conditions listed in supplementary table 1 .
datasets were collected at 100k at the daresbury and diamond synchrotron light sources and processed with the ccp4 program suite .
the structures of human , rat and mouse angiotensinogen were solved by molecular replacement in phaser27 , using an ensemble of distantly related serpins as the search model with additional phase information obtained from a gdcl3 derivative of human angitensinogen .
the structure of the complex with renin was solved by molecular replacement using renin from pdb entry 2bks28 and its peptide complex from pdb entry 1smr7 .
further details related to crystal structures and refinement , recombinant expression , thiol titration and nitrosylation and the assessment of sulphydryl blockage and oxidation , the determination of redox potentials , renin kinetics and the demonstration of reduced and oxidised forms of angiotensinogen , are given in methods .
 blood pressure is critically controlled by angiotensins1 , vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen , a non - inhibitory member of the serpin family of protease inhibitors2,3 . although angiotensinogen has long been regarded as a passive substrate , the crystal structures solved here to 2.1 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 a 4.4 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 . 
 we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidised 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 . 
Methods Summary
Supplementary Material