Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism

Wei H, Cai H, Wu J, Wei Z, Zhang F, Huang X, Ma L, Feng L, Zhang R, Wang Y, Ragg H, et al. (2016)
JOURNAL OF BIOLOGICAL CHEMISTRY 291(48): 24900-24911.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Wei, Hudie; Cai, Haiyan; Wu, Jiawei; Wei, Zhenquan; Zhang, Fei; Huang, Xin; Ma, Lina; Feng, Lingling; Zhang, Ruoxi; Wang, YunjieUniBi; Ragg, HermannUniBi; Zheng, Ying
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Abstract / Bemerkung
Lamprey angiotensinogen (l-ANT) is a hormone carrier in the regulation of blood pressure, but it is also a heparin-dependent thrombin inhibitor in lamprey blood coagulation system. The detailed mechanisms on how angiotensin is carried by l-ANT and how heparin binds l-ANT and mediates thrombin inhibition are unclear. Here we have solved the crystal structure of cleaved l-ANT at 2.7 angstrom resolution and characterized its properties in heparin binding and protease inhibition. The structure reveals that l-ANT has a conserved serpin fold with a labile N-terminal angiotensin peptide and undergoes a typical stressed-to-relaxed conformational change when the reactive center loop is cleaved. Heparin binds l-ANT tightly with a dissociation constant of similar to 10 nM involving similar to 8 monosaccharides and similar to 6 ionic interactions. The heparin binding site is located in an extensive positively charged surface area around helix D involving residues Lys-148, Lys-151, Arg-155, and Arg-380. Although l-ANT by itself is a poor thrombin inhibitor with a second order rate constant of 500 M-1 s(-1), its interaction with thrombin is accelerated 90-fold by high molecular weight heparin following a bell-shaped dose-dependent curve. Short heparin chains of 6-20 monosaccharide units are insufficient to promote thrombin inhibition. Furthermore, an l-ANT mutant with the P1 Ile mutated to Arg inhibits thrombin nearly 1500-fold faster than the wild type, which is further accelerated by high molecular weight heparin. Taken together, these results suggest that heparin binds l-ANT at a conserved heparin binding site around helix D and promotes the interaction between l-ANT and thrombin through a template mechanism conserved in vertebrates.
Erscheinungsjahr
2016
Zeitschriftentitel
JOURNAL OF BIOLOGICAL CHEMISTRY
Band
291
Ausgabe
48
Seite(n)
24900-24911
ISSN
0021-9258
eISSN
1083-351X
Page URI
https://pub.uni-bielefeld.de/record/2907725

Zitieren

Wei H, Cai H, Wu J, et al. Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism. JOURNAL OF BIOLOGICAL CHEMISTRY. 2016;291(48):24900-24911.
Wei, H., Cai, H., Wu, J., Wei, Z., Zhang, F., Huang, X., Ma, L., et al. (2016). Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(48), 24900-24911. doi:10.1074/jbc.M116.725895
Wei, Hudie, Cai, Haiyan, Wu, Jiawei, Wei, Zhenquan, Zhang, Fei, Huang, Xin, Ma, Lina, et al. 2016. “Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism”. JOURNAL OF BIOLOGICAL CHEMISTRY 291 (48): 24900-24911.
Wei, H., Cai, H., Wu, J., Wei, Z., Zhang, F., Huang, X., Ma, L., Feng, L., Zhang, R., Wang, Y., et al. (2016). Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism. JOURNAL OF BIOLOGICAL CHEMISTRY 291, 24900-24911.
Wei, H., et al., 2016. Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(48), p 24900-24911.
H. Wei, et al., “Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism”, JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, 2016, pp. 24900-24911.
Wei, H., Cai, H., Wu, J., Wei, Z., Zhang, F., Huang, X., Ma, L., Feng, L., Zhang, R., Wang, Y., Ragg, H., Zheng, Y., Zhou, A.: Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism. JOURNAL OF BIOLOGICAL CHEMISTRY. 291, 24900-24911 (2016).
Wei, Hudie, Cai, Haiyan, Wu, Jiawei, Wei, Zhenquan, Zhang, Fei, Huang, Xin, Ma, Lina, Feng, Lingling, Zhang, Ruoxi, Wang, Yunjie, Ragg, Hermann, Zheng, Ying, and Zhou, Aiwu. “Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism”. JOURNAL OF BIOLOGICAL CHEMISTRY 291.48 (2016): 24900-24911.

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Daten bereitgestellt von Europe PubMed Central.

Structural basis for the specificity of renin-mediated angiotensinogen cleavage.
Yan Y, Zhou A, Carrell RW, Read RJ., J Biol Chem 294(7), 2019
PMID: 30563843

63 References

Daten bereitgestellt von Europe PubMed Central.

Step-by-step evolution of vertebrate blood coagulation.
Doolittle RF., Cold Spring Harb. Symp. Quant. Biol. 74(), 2009
PMID: 19667012
The heparin binding properties of heparin cofactor II suggest an antithrombin-like activation mechanism.
O'Keeffe D, Olson ST, Gasiunas N, Gallagher J, Baglin TP, Huntington JA., J. Biol. Chem. 279(48), 2004
PMID: 15371417
Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism.
Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA., Proc. Natl. Acad. Sci. U.S.A. 99(17), 2002
PMID: 12169660
Emergence and evolution of the renin-angiotensin-aldosterone system.
Fournier D, Luft FC, Bader M, Ganten D, Andrade-Navarro MA., J. Mol. Med. 90(5), 2012
PMID: 22527880
The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity.
Dementiev A, Petitou M, Herbert JM, Gettins PG., Nat. Struct. Mol. Biol. 11(9), 2004
PMID: 15311268
Isolation of a protein Z-dependent plasma protease inhibitor.
Han X, Fiehler R, Broze GJ Jr., Proc. Natl. Acad. Sci. U.S.A. 95(16), 1998
PMID: 9689066
Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin.
Li W, Johnson DJ, Esmon CT, Huntington JA., Nat. Struct. Mol. Biol. 11(9), 2004
PMID: 15311269
The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature.
Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, Irving JA, Lomas DA, Luke CJ, Moyer RW, Pemberton PA, Remold-O'Donnell E, Salvesen GS, Travis J, Whisstock JC., J. Biol. Chem. 276(36), 2001
PMID: 11435447
A redox switch in angiotensinogen modulates angiotensin release.
Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, Stein PE, Broughton Pipkin F, Read RJ., Nature 468(7320), 2010
PMID: 20927107
Structure of native protein C inhibitor provides insight into its multiple functions.
Li W, Adams TE, Kjellberg M, Stenflo J, Huntington JA., J. Biol. Chem. 282(18), 2007
PMID: 17337440
Heparin cofactor II: discovery, properties, and role in controlling vascular homeostasis.
Rau JC, Mitchell JW, Fortenberry YM, Church FC., Semin. Thromb. Hemost. 37(4), 2011
PMID: 21805439
Alpha1-antitrypsin Pittsburgh in a family with bleeding tendency.
Hua B, Fan L, Liang Y, Zhao Y, Tuddenham EG., Haematologica 94(6), 2009
PMID: 19483159
Localization of the heparin-binding site of glia-derived nexin/protease nexin-1 by site-directed mutagenesis.
Stone SR, Brown-Luedi ML, Rovelli G, Guidolin A, McGlynn E, Monard D., Biochemistry 33(24), 1994
PMID: 8011637
Characterization of the heparin-binding site of the protein z-dependent protease inhibitor.
Yang L, Ding Q, Huang X, Olson ST, Rezaie AR., Biochemistry 51(19), 2012
PMID: 22540147
Antithrombins Wibble and Wobble (T85M/K): archetypal conformational diseases with in vivo latent-transition, thrombosis, and heparin activation.
Beauchamp NJ, Pike RN, Daly M, Butler L, Makris M, Dafforn TR, Zhou A, Fitton HL, Preston FE, Peake IR, Carrell RW., Blood 92(8), 1998
PMID: 9763552
Exosite determinants of serpin specificity.
Gettins PG, Olson ST., J. Biol. Chem. 284(31), 2009
PMID: 19401470
Glycosaminoglycan-mediated leuserpin-2/thrombin interaction. Structure-function relationships.
Ragg H, Ulshofer T, Gerewitz J., J. Biol. Chem. 265(36), 1990
PMID: 2266131
Thrombin as procoagulant and anticoagulant.
Di Cera E., J. Thromb. Haemost. 5 Suppl 1(), 2007
PMID: 17635727
Serpins as hormone carriers: modulation of release.
Carrell R, Qi X, Zhou A., Meth. Enzymol. 501(), 2011
PMID: 22078532
Origin of serpin-mediated regulation of coagulation and blood pressure.
Wang Y, Koster K, Lummer M, Ragg H., PLoS ONE 9(5), 2014
PMID: 24840053
Serpins in thrombosis, hemostasis and fibrinolysis.
Rau JC, Beaulieu LM, Huntington JA, Church FC., J. Thromb. Haemost. 5 Suppl 1(), 2007
PMID: 17635716
Serpin-glycosaminoglycan interactions.
Rein CM, Desai UR, Church FC., Meth. Enzymol. 501(), 2011
PMID: 22078533
Thrombin inhibition by the serpins.
Huntington JA., J. Thromb. Haemost. 11 Suppl 1(), 2013
PMID: 23809129
Use of TLS parameters to model anisotropic displacements in macromolecular refinement.
Winn MD, Isupov MN, Murshudov GN., Acta Crystallogr. D Biol. Crystallogr. 57(Pt 1), 2001
PMID: 11134934
The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop.
Zhou A, Carrell RW, Huntington JA., J. Biol. Chem. 276(29), 2001
PMID: 11325972
Genomic evidence for a simpler clotting scheme in jawless vertebrates.
Doolittle RF, Jiang Y, Nand J., J. Mol. Evol. 66(2), 2008
PMID: 18283387
Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6-A structure of the heparin-bridged complex.
Li W, Adams TE, Nangalia J, Esmon CT, Huntington JA., Proc. Natl. Acad. Sci. U.S.A. 105(12), 2008
PMID: 18362344
Identification of the antithrombin III heparin binding site.
Ersdal-Badju E, Lu A, Zuo Y, Picard V, Bock SC., J. Biol. Chem. 272(31), 1997
PMID: 9235938
Does the renin-angiotensin system participate in regulation of human vasculogenesis and angiogenesis?
Khakoo AY, Sidman RL, Pasqualini R, Arap W., Cancer Res. 68(22), 2008
PMID: 19010879
Ovalbumin and angiotensinogen lack serpin S-R conformational change.
Stein PE, Tewkesbury DA, Carrell RW., Biochem. J. 262(1), 1989
PMID: 2818556
Antiangiogenic forms of antithrombin specifically bind to the anticoagulant heparin sequence.
Schedin-Weiss S, Richard B, Hjelm R, Olson ST., Biochemistry 47(51), 2008
PMID: 19035835
Likelihood-enhanced fast translation functions.
McCoy AJ, Grosse-Kunstleve RW, Storoni LC, Read RJ., Acta Crystallogr. D Biol. Crystallogr. 61(Pt 4), 2005
PMID: 15805601
The heparin binding site of protein C inhibitor is protease-dependent.
Li W, Huntington JA., J. Biol. Chem. 283(51), 2008
PMID: 18974053
Serpin structure, function and dysfunction.
Huntington JA., J. Thromb. Haemost. 9 Suppl 1(), 2011
PMID: 21781239
The CCP4 suite: programs for protein crystallography.
Collaborative Computational Project, Number 4., Acta Crystallogr. D Biol. Crystallogr. 50(Pt 5), 1994
PMID: 15299374
An unexpected link between angiotensinogen and thrombin.
Wang Y, Ragg H., FEBS Lett. 585(14), 2011
PMID: 21722639
Serpin structure, mechanism, and function.
Gettins PG., Chem. Rev. 102(12), 2002
PMID: 12475206
On the target specificity of plasminogen activator inhibitor 1: the role of heparin, vitronectin, and the reactive site.
Keijer J, Linders M, Wegman JJ, Ehrlich HJ, Mertens K, Pannekoek H., Blood 78(5), 1991
PMID: 1715220
Coot: model-building tools for molecular graphics.
Emsley P, Cowtan K., Acta Crystallogr. D Biol. Crystallogr. 60(Pt 12 Pt 1), 2004
PMID: 15572765
Met 358 to Arg mutation of alpha 1-antitrypsin associated with protein C deficiency in a patient with mild bleeding tendency.
Vidaud D, Emmerich J, Alhenc-Gelas M, Yvart J, Fiessinger JN, Aiach M., J. Clin. Invest. 89(5), 1992
PMID: 1569192
Allosteric modulation of hormone release from thyroxine and corticosteroid-binding globulins.
Qi X, Loiseau F, Chan WL, Yan Y, Wei Z, Milroy LG, Myers RM, Ley SV, Read RJ, Carrell RW, Zhou A., J. Biol. Chem. 286(18), 2011
PMID: 21325280
Helix D elongation and allosteric activation of antithrombin.
Belzar KJ, Zhou A, Carrell RW, Gettins PG, Huntington JA., J. Biol. Chem. 277(10), 2001
PMID: 11741963
Heparin cofactor II.
Tollefsen DM., Adv. Exp. Med. Biol. 425(), 1997
PMID: 9433487
The anticoagulant activation of antithrombin by heparin.
Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW., Proc. Natl. Acad. Sci. U.S.A. 94(26), 1997
PMID: 9405673
Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes.
Ragg H, Kumar A, Koster K, Bentele C, Wang Y, Frese MA, Prib N, Kruger O., BMC Evol. Biol. 9(), 2009
PMID: 19698129
Heparin is a major activator of the anticoagulant serpin, protein Z-dependent protease inhibitor.
Huang X, Rezaie AR, Broze GJ Jr, Olson ST., J. Biol. Chem. 286(11), 2011
PMID: 21220417
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