Altered native stability is the dominant basis for susceptibility of a1-antitrypsin mutants to polymerization

Biochemical Journal

Volumn 460, Issue 1, 2014, Pages 103-115

  Irving, James A ^a   Haq, Imran ^b   Dickens, Jennifer A ^a   Faull, Sarah V ^a   Lomas, David A ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Cirrhosis; Denaturation; Disulfide; Polymerization; Serpin; Stability

Indexed keywords

ALPHA 1 ANTITRYPSIN; MONOCLONAL ANTIBODY; MUTANT PROTEIN;

ARTICLE; CONCENTRATION (PARAMETERS); CONFORMATIONAL TRANSITION; DENSITOMETRY; DISULFIDE BOND; IN VITRO STUDY; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DENATURATION; PROTEIN EXPRESSION; PROTEIN POLYMERIZATION; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; PROTEIN UNFOLDING; QUANTUM YIELD; TEMPERATURE; TEMPERATURE DEPENDENCE; THERMOSTABILITY; TRANSITION TEMPERATURE;

ALPHA 1-ANTITRYPSIN; AMINO ACID SUBSTITUTION; ANIMALS; CATTLE; CHYMOTRYPSIN; CIRCULAR DICHROISM; POINT MUTATION; POLYMERIZATION; PROTEIN STABILITY; RECOMBINANT PROTEINS; RETROSPECTIVE STUDIES; TEMPERATURE;

EID: 84899424699     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20131650     Document Type: Article

References (62)

1. Silverman, G. A., Bird, P. I., Carrell, R. W., Church, F. C., Coughlin, P. B., Gettins, P., Irving, J., Lomas, D. A., Moyer, R. W., Pemberton, P. et al. (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, novel functions, mechanism of inhibition and a revised nomenclature. J. Biol. Chem. 276, 33293-33296
2. Irving, J. A., Steenbakkers, P. J. M., Lesk, A. M., Op den Camp, H. J. M., Pike, R. N. and Whisstock, J. C. W. (2002) Serpins in prokaryotes. Mol. Biol. Evol. 19, 1881-1890
3. Anfinsen, C. B. (1973) Principles that govern the folding of protein chains. Science 181, 223-230
4. Whisstock, J. C. and Bottomley, S. P. (2006) Molecular gymnastics, serpin structure, folding and misfolding. Curr. Opin. Struct. Biol. 16, 761-768
5. Stein, P. E. and Carrell, R. W. (1995) What do dysfunctional serpins tell us about molecular mobility and disease? Nat. Struct. Biol. 2, 96-113
6. Lomas, D. A., Evans, D. L., Finch, J. T. and Carrell, R. W. (1992) The mechanism of Z a1-antitrypsin accumulation in the liver. Nature 357, 605-607
7. Lomas, D. A., Finch, J. T., Seyama, K., Nukiwa, T. and Carrell, R. W. (1993) a1-Antitrypsin Siiyama (Ser53?Phe). Further evidence for intracellular loop-sheet polymerization. J. Biol. Chem. 268, 15333-15335
8. Mast, A. E., Enghild, J. J. and Salvesen, G. (1992) Conformation of the reactive site loop of a1-proteinase inhibitor probed by limited proteolysis. Biochemistry 31, 2720-2728
9. Elliott, P. R., Bilton, D. and Lomas, D. A. (1998) Lung polymers in Z a1-antitrypsin deficiency-related emphysema. Am. J. Respir. Cell Mol. Biol. 18, 670-674
10. Lomas, D. A. and Mahadeva, R. (2002) a1-Antitrypsin polymerisation and the serpinopathies: pathobiology and prospects for therapy. J. Clin. Invest. 110, 1585-1590
11. Gooptu, B. and Lomas, D. A. (2008) Polymers and inflammation: disease mechanisms of the serpinopathies. J. Exp. Med. 205, 1529-1534
12. Ekeowa, U. I., Gooptu, B., Belorgey, D., Hägglöf, P., Karlsson-Li, S., Miranda, E., P?erez, J., MacLeod, I., Kroger, H., Marciniak, S. J. et al. (2009) a1-Antitrypsin deficiency, chronic obstructive pulmonary disease and the serpinopathies. Clin. Sci. 116, 837-850
13. Davis, R. L., Shrimpton, A. E., Holohan, P. D., Bradshaw, C., Feiglin, D., Collins, G. H., Sonderegger, P., Kinter, J., Becker, L. M., Lacbawan, F. et al. (1999) Familial dementia caused by polymerization of mutant neuroserpin. Nature 401, 376-379
14. Gooptu, B. and Lomas, D. A. (2009) Conformational pathology of the serpins: themes, variations and therapeutic strategies. Annu. Rev. Biochem. 78, 147-176
15. Devlin, G. L., Chow, M. K. M., Howlett, G. J. and Bottomley, S. P. (2002) Acid denaturation of a1-antitrypsin: characterization of a novel mechanism of serpin polymerization. J. Mol. Biol. 324, 859-870
16. Sivasothy, P., Dafforn, T. R., Gettins, P. G. and Lomas, D. A. (2000) Pathogenic a1-antitrypsin polymers are formed by reactive loop-β-sheet A linkage. J. Biol. Chem. 275, 33663-33668
17. Huntington, J. A., Pannu, N. S., Hazes, B., Read, R. J., Lomas, D. A. and Carrell, R. W. (1999) A 2.6A° structure of a serpin polymer and implications for conformational disease. J. Mol. Biol. 293, 449-455
18. Dunstone, M. A., Dai, W., Whisstock, J. C., Rossjohn, J., Pike, R. N., Feil, S. C., Le Bonniec, B. F., Parker, M. W. and Bottomley, S. P. (2000) Cleaved antitrypsin polymers at atomic resolution. Protein Sci. 9, 417-420
19. Krishnan, B. and Gierasch, L. M. (2011) Dynamic local unfolding in the serpin a1 antitrypsin provides a mechanism for loop insertion and polymerization. Nat. Struct. Mol. Biol. 18, 222-226
20. Nyon, M. P., Segu, L., Cabrita, L. D., Lévy, G. R., Kirkpatrick, J., Roussel, B. D., Patschull, A. O., Barrett, T. E., Ekeowa, U. I., Kerr, R. et al. (2012) Structural dynamics associated with intermediate formation in an archetypal conformational disease. Structure 20, 504-512
21. Yamasaki, M., Li, W., Johnson, D. J. and Huntington, J. A. (2008) Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature 455, 1255-1258
22. Yamasaki, M., Sendall, T. J., Pearce, M. C., Whisstock, J. C. and Huntington, J. A. (2011) Molecular basis of a1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep. 12, 1011-1017
23. Powell, L. M. and Pain, R. H. (1992) Effects of glycosylation on the folding and stability of human, recombinant and cleaved a1-antitrypsin. J. Mol. Biol. 224, 241-252
24. James, E. L., Whisstock, J. C., Gore, M. G. and Bottomley, S. P. (1999) Probing the unfolding pathway of a1-antitrypsin. J. Biol. Chem. 274, 9482-9488
25. Lomas, D. A., Evans, D. L., Stone, S. R., Chang, W. S. and Carrell, R. W. (1993) Effect of the Z mutation on the physical and inhibitory properties of a1-antitrypsin. Biochemistry 32, 500-508
26. Miranda, E., Perez, J., Ekeowa, U. I., Hadzic, N., Kalsheker, N., Gooptu, B., Portmann, B., Belorgey, D., Hill, M., Chambers, S. et al. (2010) A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with a1-antitrypsin deficiency. Hepatology 52, 1078-1088
27. Ekeowa, U. I., Freeke, J., Miranda, E., Gooptu, B., Bush, M. F., Perez, J., Teckman, J., Robinson, C. V. and Lomas, D. A. (2010) Defining the mechanism of polymerization in the serpinopathies. Proc. Natl. Acad. Sci. U.S.A. 107, 17146-17151
28. Dafforn, T. R., Mahadeva, R., Elliott, P. R., Sivasothy, P. and Lomas, D. A. (1999) A kinetic mechanism for the polymerization of a1-antitrypsin. J. Biol. Chem. 274, 9548-9555
29. Gilis, D., McLennan, H. R., Dehouck, Y., Cabrita, L. D., Rooman, M. and Bottomley, S. P. (2003) In vitro and in silico design of a1-antitrypsin mutants with different conformational stabilities. J. Mol. Biol. 325, 581-589
30. Chang, W. S., Whisstock, J. C., Hopkins, P. C., Lesk, A. M., Carrell, R. W. and Wardell, M. R. (1997) Importance of the release of strand 1C to the polymerization mechanism of inhibitory serpins. Protein Sci. 6, 89-98
31. Baek, J. H., Im, H., Kang, U. B., Seong, K. M., Lee, C., Kim, J. and Yu, M. H. (2007) Probing the local conformational change of a1-antitrypsin. Protein Sci. 16, 1842-1850
32. Fass, D. (2012) Disulfide bonding in protein biophysics. Annu. Rev. Biophys. 41, 63-79
33. Chow, M. K. M., Devlin, G. L. and Bottomley, S. P. (2001) Osmolytes as modulators of conformational changes in the serpins. Biol. Chem. 382, 1593-1599
34. Sharp, L. K., Mallya, M., Kinghorn, K. J., Wang, Z., Crowther, D. C., Huntington, J. A., Belorgey, D. and Lomas, D. A. (2006) Sugar and alcohol molecules provide a therapeutic strategy for the serpinopathies that cause dementia and cirrhosis. FEBS J. 273, 2540-2552
35. Devlin, G. L., Parfrey, H., Tew, D. J., Lomas, D. A. and Bottomley, S. P. (2001) Prevention of polymerization of M and Z a1-antitrypsin (a1-AT) with trimethylamine N-oxide. Implications for the treatment of a1-AT deficiency. Am. J. Respir. Cell Mol. Biol. 24, 727-732
36. Haq, I., Irving, J. A., Faull, S. V., Dickens, J. A., Ordonez, A., Belorgey, D., Gooptu, B. and Lomas, D. A. (2013) Reactive centre loop mutants of a1-antitrypsin reveal position-specific effects on intermediate formation along the polymerization pathway. Biosci. Rep. 33, e00046
37. Hoops, S., Sahle, S., Gauges, R., Lee, C., Pahle, J., Simus, N., Singhal, M., Xu, L., Mendes, P. and Kummer, U. (2006) COPASI: a COmplex PAthway SImulator. Bioinformatics 22, 3067-3074
38. Zhou, A., Carrell, R. W. and Huntington, J. A. (2001) The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop. J. Biol. Chem. 276, 27541-27547
39. Im, H., Seo, E. J. and Yu, M.-H. (1999) Metastability in the inhibitory mechanism of human a1-antitrypsin. J. Biol. Chem. 274, 11072-11077
40. Riener, C. K., Kada, G. and Gruber, H. J. (2002) Quick measurement of protein sulfhydryls with Ellman's reagent and with 4,4'dithiodipyridine. Anal. Bioanal. Chem. 373, 266-276
41. Nettleship, J. E., Brown, J., Groves, M. R. and Geerlof, A. (2008) Methods for protein characterization by mass spectrometry, thermal shift (ThermoFluor) assay, and multiangle or static light scattering. Methods Mol. Biol. 426, 299-318
42. Lawrence, D. A., Olson, S. T., Palaniappan, S. and Ginsburg, D. (1994) Engineering plasminogen activator inhibitor 1 mutants with increased functional stability. Biochemistry 33, 3643-3648
43. Reference deleted
44. Zhou, A. and Carrell, R. W. (2008) Dimers initiate and propagate serine protease inhibitor polymerisation. J. Mol. Biol. 375, 36-42
45. Friedler, A., Veprintsev, D. B., Hansson, L. O. and Fersht, A. R. (2003) Kinetic instability of p53 core domain mutants: implications for rescue by small molecules. J. Biol. Chem. 278, 24108-24112
46. Reference deleted
47. Kezdy, F. J. and Kaiser, E. T. (1970) Principles of active site titration of proteolytic enzymes. Methods Enzymol. 19, 3-20
48. Hopkins, P. C., Carrell, R. W. and Stone, S. R. (1993) Effects of mutations in the hinge region of serpins. Biochemistry 32, 7650-7657
49. Parfrey, H., Mahadeva, R., Ravenhill, N. A., Zhou, A., Dafforn, T. R., Foreman, R. C. and Lomas, D. A. (2003) Targeting a surface cavity of a1-antitrypsin to prevent conformational disease. J. Biol. Chem. 278, 33060-33066
50. Knaupp, A. S., Keleher, S., Yang, L., Dai, W., Bottomley, S. P. and Pearce, M. C. (2013) The roles of helix I and strand 5A in the folding, function and misfolding of a1-antitrypsin. PLoS ONE 8, e54766
51. Knaupp, A. S. and Bottomley, S. P. (2011) Structural change in beta-sheet A of Z a1-antitrypsin is responsible for accelerated polymerization and disease. J. Mol. Biol. 413, 888-898
52. Cabrita, L. D., Dai, W. and Bottomley, S. P. (2004) Different conformational changes within the F-helix occur during serpin folding, polymerization and proteinase inhibition. Biochemistry 43, 9834-9839
53. Pace, C. N. and Scholtz, J. M. (1997) Measuring the conformational stability of a protein. In Protein Structure: A Practical Approach (Creighton, T. E., ed.), pp. 299-321, Oxford University Press, Oxford
54. Niesen, F. H., Berglund, H. and Vedadi, M. (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2, 2212-2221
55. Koloczek, H., Banbula, A., Salvesen, G. S. and Potempa, J. (1996) Serpin a1-proteinase inhibitor probed by intrinsic tryptophan fluorescence spectroscopy. Protein Sci. 5, 2226-2235
56. Sanchez-Ruiz, J. M. (2010) Protein kinetic stability. Biophys. Chem. 148, 1-15
57. Cox, D. W., Billingsley, G. D. and Callahan, J. W. (1986) Aggregation of plasma Z type a1-antitrypsin suggests basic defect for the deficiency. FEBS Lett. 205, 255-260
58. Harries, D. and Rosgen, J. (2008) A practical guide on how osmolytes modulate macromolecular properties. Methods Cell Biol. 84, 679-735
59. Costas, M., Rodriguez-Larrea, D., De Maria, L., Borchert, T. V., Gomez-Puyou, A. and Sanchez-Ruiz, J. M. (2009) Between-species variation in the kinetic stability of TIM proteins linked to solvation-barrier free energies. J. Mol. Biol. 385, 924-937
60. Simonovic, I. and Patston, P. A. (2000) The native metastable fold of C1-inhibitor is stabilized by disulfide bonds. Biochim. Biophys. Acta 1481, 97-102
61. Gooptu, B., Miranda, E., Nobeli, I., Mallya, M., Purkiss, A., Leigh Brown, S. C., Summers, C., Phillips, R. L., Lomas, D. A. and Tracey, B. E. (2009) Crystallographic and cellular characterisation of two mechanisms stabilising the native fold of a1-antitrypsin: implications for disease and drug design. J. Mol. Biol. 387, 857-868
62. Elliott, P. R., Pei, X. Y., Dafforn, T. R. and Lomas, D. A. (2000) Topography of a 2.0A° structure of a1-antitrypsin reveals targets for rational drug design to prevent conformational disease. Protein Sci. 9, 1274-1281