The biostructural pathology of the serpins: Critical function of sheet opening mechanism

Biological Chemistry Hoppe-Seyler

Volumn 377, Issue 1, 1996, Pages 1-17

  Carrell, Robin W ^a   Stein, Penelope E ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

1 antitrypsin; Angiotensinogen; Antithrombin; PAI 1; Serpins

Indexed keywords

ANGIOTENSINOGEN; SERINE PROTEINASE INHIBITOR;

COMPARATIVE STUDY; DNA TEMPLATE; HUMAN; MUTATION; NONHUMAN; PATHOLOGY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN STABILITY; PROTEIN STRUCTURE; REVIEW; STRUCTURE ACTIVITY RELATION; VASCULAR DISEASE;

ANIMALS; GENETIC DISEASES, INBORN; HUMANS; PROTEIN CONFORMATION; SERPINS;

EID: 0030062157     PISSN: 01773593     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (98)

1. Aertgeerts, K., De Bondt, H.L., De Ranter, C.J.,and Declerck, P.J. (1995). Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor 1. Nature Structural Biology 2,891-897.
2. Bathurst, I.C., Brennan, S.O., Carrell, R.W., Cousens, L.-S., Brake, A.J.,and Barr, P.J. (1987). Yeast KEX2 protease has the properties of a human proalbumin converting enzyme. Science 235,348-350.
3. Berkenpas, M.B., Lawrence, D.A., and Ginsburg, D. (1995). Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBO J. 14,2969-2977.
4. Björk, I., Nordling, K., and Oison, S.T. (1993). Immunologie evidence for insertion of the reactive-bond loop of antithrombin into the A -sheet of the inhibitor during trapping of target proteinases. Biochemistry 32,6501-6505.
5. Blinder, MA, anderson, T.R., Abilgaard, U., and Tollefsen, D.M. (1989). Heparin cofactor II Oslo: mutation of Arg 189 to His decreases the affinity for dermatan sulphate. J. Biol. Chem. 264, 5128-5133.
6. Bock, S.C., Silberman, J.A., Wikoff, W., Abildgaard, U., and Hultin, M.B. (1989). Identification of a threonine for alanine substitution at residue 404 of antithrombin III Oslo suggests integrity of the 404-407 region is improtant for maintaining normal inhibitor levels. Thromb. Haemost. 62,494.
7. Bode, W., and Huber, R. (1991). Ligand binding: proteinase-protein inhibitor interactions. Curr. Opin. Struc. Biol. 1,45-52.
8. Bode, W., and Huber, R. (1994). Proteinase-protein inhibitor interactions. Fibrinolysis 8,161-171.
9. Borg, J.Y., Owen, M.C., Soria, C., Soria, J., Caen, J., and Carrell, R.W. (1988). Proposed heparin binding site in antithrombin based on Arginine 47. A new variant Rouen-ll, 47 Arg to His. J. Clin. Invest. 81,1292-1296.
10. Boswell, D.R., Owen, M.C., Brennan, S.O., Carrell, R.W., and McLachlan, A.D. (1980). Homology of a,-Antitrypsin and antithrombin-lll: Identification of active sites. XXVIIth Colloquium Protides of the Biological Fluids (Brussels) (Oxford, UK: Pergamon Press Ltd.), 23, pp. 129-132.
11. Brantly, M., Nukiwa.T., and Crystal, R.G. (1988). Molecular basis of c-antitrypsin deficiency. Am. J. Med. 84 (suppl6A), 13-31.
12. Bruce, D., Perry, D.J., Borg, J.-Y, Carrell, R.W., and Wardell, M.R. (1994). Thromboembolic disease due to thermolabile confor-mational changes of antithrombin Rouen VI (187 AsnAsp). J. Clin. Invest. 94,2265-2274.
13. Bruch, M., Weiss, V., and Engel, J. (1988). Plasma serine proteinase inhibitors (serpins) exhibit major conformational changes and a large increase in conformational stability upon cleavage of their reactive sites. J. Biol. Chem. 263, 1662616630.
14. Carrell, R., Owen, M., Brennan, S.,andVaughan, L. (1979). Carboxy terminal fragment of human a-1-antitrypsin from hydroxylamine cleavage: homology with antithrombin III. Biochem. Biophys. Res. Commun. 91,1032-1037.
15. Carrell, R.W., and Owen, M.C. (1985). Plakalbumin, arantitrypsin, antithrombin and the mechanism of inflammatory thrombosis. Nature 317,730-732.
16. Carrell, R., and Travis, J. (1985). ctrantitrypsin and the serpins: variation and countervariation. Trends Biochem. Sei. 10, 2024.
17. Carrell, R.W., Jeppsson, J.-O., Laurell, C.-B., Brennan, S.O., Owen, M.C., Vaughan, L, and Boswell, D.R. (1982). Structure and variation of human arantitrypsin. Nature 298,329-334.
18. Carrell, R.W., Evans, D.L, and Stein, P.E. (1991). Mobile reactive centre of serpins and the control of thrombosis. Nature 353, 576-578.
19. Carrell, R.W., Evans, D.U., and Stein, P.E. (1993). Corrigendum: Mobile reactive centre of serpins and the control of thrombosis. Nature 364,737.
20. Carrell, R.W., Stein, P.E., Fermi, Q., and Wardell, M.R. (1994). Biological Implications of a 3A Structure of Dimeric Antithrombin. Nature Structural Biology 2,257-270.
21. Caulfield, M., Lavender, P., Farrall, M., Munroe, P., Lawson, M., Turner, P., and Clark, A.J. (1994). Linkage of the angiotensinogen gene to essential hypertension. N. Engl. J. Med. 330, 1629-1633.
22. Choay, J., Petitou, M., Lormeau, J.C., Sinay, P., Casu, B., and Gatti, G. (1983). Structure activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem. Biophys. Res. Commun. 116,492-499.
23. Cox, D.W., Billingsley, G.D., and Callahan, J.W. (1986). Aggregation of plasma Z type a(-antitrypsin suggests basic defect for the deficiency. FEBS Lett. 205,255-260.
24. Crowther, D.C., Evans, D.L, and Carrell, R.W. (1992). Serpins: implications of a mobile reactive centre. Curr. Opin. Biotechnology 3,399-407.
25. Davis III, A.E., Aulak, K., Parad, R.B., Stecklein, H.P., Eidering, E., Hack, C.E., Kramer, J., Strunk, R.C., Bissler, J., and Rosen, F.S. (1992). C1 inhibitor hinge region mutations produce dysfunction by different mechanisms. Nature Genetics 1,354-358.
26. Declerck, P.J., De Mol, M., Baudner, S., Pâques, E.P., Preissner, K.T., Muller-Berghaus, G., and Collen, D. (1988). Purification and characterisation of a plasminogen activator 1 binding protein from human plasma. Identification as a multimeric form of S protein vitronectin. J. Biol. Chem. 263,15454-15461.
27. Devraj-Kizuk, R., Chui, O.H.K., Prochownik, E.V., Carter, C.J., Ofosu, F.A., and Blajchman, M.A. (1988). Antithrombin IllHamilton: a gene with a point mutation (guanine to adenine) in codon 382 causing impaired serine protease reactivity. Blood 72,1518-1523.
28. Eitzman, D.T., Fay, W.P., Lawrence, D.A., Francis-Chmura, A.M., Shore, J.D., Olson, S.T., and Ginsburg, D. (1995). Peptide mediated inactivation of recombinant and platelet plasminogen activator inhibitor-1 In Vitro. J. Clin. Invest. 95,2416-2420.
29. Eldering, E., Verpy, E., Roem, D., Meo.T, andTosi, M. (1995). Cterminal substitutions in the serpin C1 -inhibitor that cause loop overinsertion and subsequent multimerization. J. Biol. Chem. 270,2579-2587.
30. Engh, R.A., Wright, HT., and Huber, R. (1990). Modeling the intact form of the a,-proteinase inhibitor. Prat. Engng. 3,469-477.
31. Engh, R., Huber, R., Bode, W., and Schulze, A. (1995). Divining the serpin inhibition mechanism: a suicide substrate 'springe'? Trends in Biotech. 73,503-510.
32. Eriksson, S., Carlson, J., and Vêlez, R. (1986). Risk of cirrhosis and primary liver cancer in alphai-antitrypsin deficiency. N. Eng. J. Med. 314,736-739.
33. Gettins, P. (1989). Absence of large scale proteolytic change upon limited proteolysis of ovalbumin, the prototypic serpin. J. Biol. Chem. 264,3781 -3785.
34. Hekman, C.M., and Loskutoff, D.U. (1985). Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by dénaturants. J. Biol. Chem. 260,11581-11587.
35. Holmes, M.D., Brantly, M.L, Fells, G.A., and Crystal, R.G. (1990). a,-antitrypsin Whesda: molecular basis of an unusual arantitrypsin deficiency variant. Biochem. Biophys. Res. Commun. 170,1013-1020.
36. Huber, R., and Carrell, R.W. (1989). Implications of the three-dimensional structure of a,-antitrypsin for structure and function of serpins. Biochemistry 28,8951-8966.
37. Hunt, L.T., and Dayhoff, M.O. (1980). A surprising new protein superfamily containing ovalbumin, antithrombin-lll, and alpharproteinase inhibitor. Biochem. Biophys. Res. Commun. 95,864-871.
38. Huntington, J.A., Patson, P.A., and Gettins, P.G.W. (1995). S-ovalbumin, an ovalbumin conformer with properties analogous to those of loop-inserted serpins. Protein Science 4,613-621.
39. Jeppsson, J.-O. (1976). Amino acid substitution Glu-Lys in a,-antitrypsin PiZ. FEBS Lett. 65,195-197.
40. Jeppsson, J.-O., Larsson, C., and Eriksson, S. (1975). Characterization of arantitrypsin in the inclusion bodies from the liver in arantitrypsin deficiency. N. Eng. J. Med. 293,576-579.
41. Jeunemaitre, X., Soubrier, F., Kotelevtsev, Y.V., Lifton, R.P., Williams, C.S., Charru, A., Hunt, S.C., Hopkins, P.N., Williams, R.R., Lalouel, J.-M., and Corvol, P. (1992). Molecualr basis of human hypertension: role of angiotensinogen. Cell 71, 169180.
42. Katsuya, T., Koike, T.W., Sharpe, N., Jackson, R., Norton, R., Horiuchi, M., Pratt, R., Dzau, V.J., and MacMahon, S. (1995). Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. Lancet 345, 16001603.
43. Kim, J., Lee, K.M., Yi, G.-S.,andYu, M.-H. (1995). A thermostable mutation located at the hydrophobia core of arantitrypsin suppresses the folding defect of the Z-type variant. J. Biol. Chem. 270,8597-8601.
44. Koide, T., Odani, S., Takahashi, K., Onon, T., and Sakuragawa, N. (1984). Antithrombin HIToyama: replacement of Arginine 47 by Cysteine in hereditary abnormal antithrombin III that lacks heparin binding ability. Proc. Nat. Acad. Sei. USA 81,289-293.
45. Kraulis, P. (1991). Molscript: a program to produce both detailed and schematic plots of proteins. J. appl. Crystallog. 24,946950.
46. Kwon, K.-S., Kim, J., Shin, H.S., and Yu, M.-H. (1994). Single amino acid substitutions of arantitrypsin that confer enhancement in thermal stability. J. Biol. Chem. 269,9627-9631.
47. Lane, DA, Olds, R.J., Boisclair, M., Chowdhury, V, Thein, S.L., Cooper, D.N., Blajchman, M., Perry, D., Emmerich, J., and Aiach, M. (1993). Antithrombin III mutation database: first update. Thrombosis and Haemostasis 70,361-369.
48. Lawrence, D.A., S.T., O., Palaniappan, S., and Ginsburg, D. (1994). Serpin reactive-center loop mobility is required for inhibitor function but not for enzyme recognition. J. Biol. Chem. 269,27657-27662.
49. Laskowski, M., Jr. and Kato, I. (1980). Protein inhibitors of pro-teinases. Ann. Rev. Biochem. 49,593-626.
50. Laurell, C.-B., and Eriksson, S. (1963). The electrophoretic a,globulin pattern of serum in arantitrypsin deficiency. Scand. J. Clin. Lab. Invest. 15,132-140.
51. Laurell, C.-B., and Jeppsson, J.-O. (1975). Proteinase inhibitors in plasma. The Plasma Proteins. Putnam, (New York, San Francisco, London: Academic Press), pp. 229-265.
52. Le, A., Graham, K.S., and Sifers, R.N. (1990). Intracellular degradation of the transport-impaired human PiZ arantitrypsin variant. Biochemical mapping of the degradative event among compartments in the secretory pathway. J. Biol. Chem. 265, 14001-14007.
53. Levin, E.G. (1986). Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells. Blood 67,1309-1313.
54. Lewis, J.H., lammarino, P.M. Spero, J.A., and Hasiba, U. (1978). Antithrombin Pittsburgh: An cti-antitrypsin variant causing hemorrhagic disease. Blood 51,129-137.
55. Lindahl, U.,Thunberg, L, Bäckstrom, G. Riesenfeld, J., Nordling, K., and Björk, J. (1984). Extension and structural variability of the antithrombin binding sequence in heparin. J. Biol. Chem. 259,12368-12376.
56. Undo, V.S., Kakkar, V.V., Learmonth, M., Melissari, E., Zappacosta, R, Panico, M., and Morris, H.R. (1995). AnithrombinTRI (Ala382 to Thr) causing severe thromboembolic tendency undergoes the S-to-R transition and is associated with a plasma-inactive high-molecular-weight complex of aggregated antithrombin. Br. J. Haematol. 89,589-601.
57. Loebermann, H., Tokuoka, R., Deisenhofer, J., and Huber, R. (1984). Human arproteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J. Mol. Biol. 777; 531-556.
58. Lomas, D.A., Evans, D.L., Finch, J.T., and Carrell, R.W. (1992).The mechanism of Z at-antitrypsin accumulation in the liver. Nature 357,605-607.
59. Lomas, D.A., Evans, D.L, Stone, S.R., Chang, W.-S.W., and Carrell, R.W. (1993). The effect of the Z mutation on the physical and inhibitory properties of a,-antitrypsin. Biochemistry 32, 500-508.
60. Lomas, D.A., Finch, J.T., Seyama, K., Nukiwa.T., and Carrell, R.W. (1993). arantitrypsin Siiyama (Ser-Phe); further evidence for intracellular loop-sheet polymerisation. J. Biol. Chem. 268, 15333-15335.
61. Lomas, DA, Elliott, P.R., Chang, W.-S.W, Wardell, M.R., and Carrell, R.W (1995a). Preparation and characterisation of latent a,-antitrypsin. J. Biol. Chem. 270,5282-5288.
62. Lomas, D.A., Elliott, P.R., Sidhar, S.K., Foreman, R.C., Finch, J.T., Cox, D.W., and Carrell, R.W. (1995b). a-antitrypsin Mmalton PPhe deleted) forms loop-sheet polymers in vivo: evidence for the C sheet mechanism of polymerisation. J. Biol. Chem. 270, 16864-16870.
63. Mahoney, W.C., Kurachi, K., and Hermodson, M.A. (1980). Formation and dissociation of the covalent complexes between trypsin and two homologous inhibitors ai-antitrypsin and antithrombin III. Eur. J. Biochem. 705,1579-1585.
64. Marshall, C.J. (1993). Evolutionary relationships among the serpins. Phil. Trans. R. Soc. Lond. B. 342,101-119.
65. Mast, A.E., Enghild, J.J., and Salvesen, G. (1992). Conformation of the reactive site loop of arproteinase inhibitor probed by limited proteolysis. Biochemistry 31,2720-2728.
66. Mikus, P., Urano.T., Liljestrom, P., and Ny,T. (1993). Plasminogenactivator inhibitor type 2 (PAl-2) is a spontaneously polymerising SERPIN. Biochemical characterisation of the recombinant intracellular and extra-cellular forms. Eur. J. Biochem. 218, 1071-1082.
67. Motionen, J., Strand, A., Symersky, J., Sweet, R.M., Danley, D.E., Geoghegan, K.F., Gerard, R.D., and Goldsmith, E.J. (1992). Structural basis of latency in plasminogen activator inhibitor-1. Nature 355,270-273.
68. Mourey, L, Samama, J.-R, Delarue, M., Petitou, M., Choay, J., and Moras, D. (1993). Crystal structure of cleaved bovine antithrombin III at 3.2 A resolution. J. Mol. Biol. 232,223-241.
69. Owen, M.C., Brennan, S.O., Lewis, J.H., and Carrell, R.W. (1983). Mutation of antitrypsin to antithrombin. ai-antitrypsin Pittsburg (358 Met to Arg), a fatal bleeding disorder. N. Eng. J. Med. 309,694-698.
70. Owen, M.C., Borg, J.Y., Soria, C., Soria, J., Caen, J., and Carrell, R.W. (1987). Heparin binding defect in a new antithrombin III variant: Rouen, 47 Arg to His. Blood 5,1275-1279.
71. Patston, P.A., Hauert, J., Michaud, M., and Schapira, M. (1995). Formation and properties of C1 -inhibitor polymers. FEBS Lett. 363,401-404.
72. Perkins, S.J., Smith, K.F., Nealis, A.S., Haris, P.I., Chapman, D., Bauer, C., and Harrison, R.A. (1992). Secondary structure changes stabilize the reactive-centre cleaved form of SERPINs. A study by 1H nuclear magnetic resonance and Fourier transform infrared spectroscopy. J. Mol. Biol. 229,1235-1254.
73. Perry, D.U., Daly, M., Harper, P.L.Tait, R.C., Price, J., Walker, I.D., and Carrell, R.W. (1991). Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of the reactive centre loop in the inhibitory function of the serpins. FEBS Lett. 235,248-250.
74. Perutz, M.F., Kendrew, J.C., and Watson, H.C. (1965). Structure and function of haemoglobin II. Some relations between polypeptide chain configuration and amino acid sequence. J. Mol. Biol. 13,669-678.
75. Petersen, E.E., Dudek-Wojciechowska, G., Sottrup-Jensen, L., and Magnusson, S. (1979). The primary structure of antithrombin III (heparin cofactor). Partial homology between alpha-1antitrypsin and antithrombin 111. The Physiological Inhibitors of Coagulation and Fibrinolysis. D. Collen, B. Wimas and M. Verstraete, eds. (Amsterdam, The Netherlands: Elsevier - North Holland Biomédical Press), pp. 43-54.
76. Peterson, C.B., Noyes, C.M., Pecon, J.M., Church, F.C., and Blackburn, M.N. (1987). Identification of a lysyl residue in antithrombin which is essential for heparin binding. J. Biol. Chem. 262,8061-8065.
77. Poller, W, Faber, J.-R, Weidinger, S., Tief, K.S.S., Fischer, M., Olek, K., Kirchgessner, M., and Heidtmann, H.-H. (1993). A leucine-to-proline substitution causes a defective oi-antichymotrypsin allele associated with familial obstructive lung disease. Genomics 17,740-743.
78. Potempa, J., Korzus, E.,andTravis, J. (1994). The serpin family of proteinase inhibitors: structure function and regulation. J. Biol. Chem. 269,15957-15960.
79. Schreuder, H.A., de Boer, B., Dijkema, R., Mulders, J., Theunissen, H.J.M., Grootenhuis, P.D.J., and Hol, W.G.J. (1994).The intact and cleaved human antithrombin III complex as a model for serin-proteinase interactions. Nature struct. Biol. 1,48-54.
80. Schulze, A.J., Baumann, U., Knof, S., Jaeger, E., Huber, R., and Laurell, C.-B. (1990). Structural transition of arantitrypsin by a peptide sequentially similar to -strand s4A. Eur. J. Biochem. 194.51-56.
81. Schulze, A.J., Frohnert, P.W., Engh, R.A., and Huber, R. (1992). Evidence for the extent of insertion of the active site loop of intact cti-proteinase inhibitor in -sheet A. Biochemistry 31, 7560-7565.
82. Shore, J.D., Day, D., Verhamme, I., Francis-Chmura, A.M., Lawrence, D., and Ginsburg, D. (1995). PAI-1 Mechanistic studies using fluorescent probes. Thrombosis and Haemostasis 73, 1008.
83. Sidhar, S.K., Lomas, D.A., Carrell, R.W., and Foreman, R.C. (1995). Mutations which impede loop/sheet polymerisation enhance the secretion of human a,-antitrypsin deficiency variants. J. Biol. Chem. 270,8393-8396.
84. Skriver, K., Wikoff, W.R., Patston, P.A., Tausk, F., Schapira, M., Kaplan, A.P., and Bock, S.C. (1991). Substrate properties of C1 inhibitor Ma (alanine 434->glutamic acid). J. Biol. Chem. 266, 9216-9221.
85. Stein, P.E., and Carrell, R.W. (1995). What do dysfunctional serpins tell us about molecular mobility and disease? Nature Struct. Biol. 2,96-113.
86. Stein, P., and Chothia, C. (1991). Serpin tertiary structure transformation. J. Mol. Biol. 227,615-621.
87. Stein, P.E., Tewkesbury, D.A., and Carrell, R.W. (1989). Ovalbumin and angiotensinogen lack serpin S-R conformational change. Biochem.J. 262,103-107.
88. Stein, P.E., Leslie, A.G.W., Finch, J.T., Turneii, W.G., McLaughlin, P.J., and Carreli, R.W. (1990). Crystal structure of ovalbumin as a model forthe reactive centre of serpins. Nature 347,99-102.
89. Stein, P.E., Leslie, A.G.W., Finch, J.T., and Carrell, R.W. (1991). Crystal structure of uncleaved ovaibumin at 1.95 A resolution. J. Mol. Biol. 227,941-959.
90. Sveger, T. (1976). Liver disease in alphai-antitrypsin deficiency detected by screening of 200000 infants. N. Eng. J. Med. 294, 1316-1321.
91. Travis, J., and Salvesen, G.S. (1983). Human plasma proteinase inhibitors. Ann. Rev. Biochem. 52, 655-709.
92. Wardell, M.R., Abrahams, J.-P., Bruce, D., Skinner, R., and Leslie, A.G.W. (1993). Crystallization and preliminary X-ray diffraction analysis of two conformations of intact human antithrombin. J. Mol. Biol. 234,1253-1258.
93. Van Baelen, H., Power, S.G.A., and Hammond, G.L. (1993). Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. Steroids 58,275-277.
94. Verpy, E., Couture-Tosi, E., Eidering, E., Lopez-Trascasa, M., Späth, P., Meo.I, andTosi, M. (1995). Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function. J. Clin. Invest. 95, 350-359.
95. Wei, A., Rubin, H., Cooperman, B.S., and Christianson, D.W. (1994). Crystal structure of an uncleaved serpin reveals the conformation of an inhibitory loop. Nature struct. Biol. 1,251 258.
96. Wilczynska, M., Fa, M., Ohlsson, P.-l., and Ny.T. (1995). The inhibition mechanism of serpins. Evidence that the mobile reactive centre loop is cleaved in the native protease-inhibitor complex. J. Biol. Chem. 270,29652-29655.
97. Wright, H.T., Qian, H.X., and Huber, R. (1990). Crystal structure of plakalbumin a proteolytically nicked form of ovalbumin. Its relationship to the structure of cleaved arproteinase inhibitor. J. -=Mol. Biol. 273,513-528.
98. Yoshida, A., Lieberman, J., Gaiduiis, L, and Ewing, C. (1976). Molecular abnormality of human alpharantitrypsin variant (PiZZ) associated with plasma activity deficiency. Proc. Natl. Acad. Sei. USA 73,1324-1328.