Functional and dysfunctional conformers of human neuroserpin characterized by optical spectroscopies and Molecular Dynamics

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1854, Issue 2, 2015, Pages 110-117

  Noto, Rosina ^a   Santangelo, Maria Grazia ^a   Levantino, Matteo ^b   Cupane, Antonio ^b   Mangione, Maria Rosalia ^a   Parisi, Daniele ^a,c,d,e   Ricagno, Stefano ^c,d   Bolognesi, Martino ^c,d   Manno, Mauro ^a   Martorana, Vincenzo ^a  

^a CNR   (Italy)

^b UNIVERSITY OF PALERMO   (Italy)

^c Department of Biosciences Institute of Biophysics CNR   (Italy)

^d UNIVERSITY OF MILAN   (Italy)

^e UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

Circular dichroism; Conformational disease; Fluorescence; Molecular Dynamics; Neuroserpin; Serpin

Indexed keywords

AROMATIC COMPOUND; GLUTAMIC ACID; ISOPROTEIN; NEUROSERPIN; POLYMER; SERINE PROTEINASE INHIBITOR; SODIUM CHLORIDE; TRYPTOPHAN; TYROSINE; NEUROPEPTIDE;

ALPHA HELIX; ARTICLE; BETA SHEET; CIRCULAR DICHROISM; COMPUTER MODEL; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; FLAME PHOTOMETRY; FLUORESCENCE SPECTROSCOPY; HYDROGEN BOND; IN VITRO STUDY; MOLECULAR DYNAMICS; POLYMERIZATION; PROTEIN ANALYSIS; PROTEIN CLEAVAGE; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN TERTIARY STRUCTURE; SPECTROSCOPY; VALIDATION STUDY; CHEMISTRY; DEMYELINATING DISEASE; GENETICS; HUMAN; METABOLISM; MYOCLONUS EPILEPSY; PATHOLOGY; PROTEIN FOLDING;

CIRCULAR DICHROISM; EPILEPSIES, MYOCLONIC; HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM; HUMANS; HYDROGEN BONDING; MOLECULAR DYNAMICS SIMULATION; NEUROPEPTIDES; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN ISOFORMS; PROTEIN STRUCTURE, SECONDARY; SERINE PROTEINASE INHIBITORS; SERPINS;

EID: 84915822554     PISSN: 15709639     EISSN: 18781454     Source Type: Journal    
DOI: 10.1016/j.bbapap.2014.10.002     Document Type: Article

References (62)

1. G.A. Hastings, T.A. Coleman, C.C. Haudenschild, S. Stefansson, E.P. Smith, R. Barthlow, S. Cherry, M. Sandkvist, D.A. Lawrence, Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival, J. Biol. Chem. 272 (1997) 33062-33067.
2. G.A. Silverman, P.I. Bird, R.W. Carrell, F.C. Church, P.B. Coughlin, P.G. Gettins, J.A. Irving, D.A. Lomas, C.J. Luke, R.W. Moyer, P.A. Pemberton, E. Remold-O'Donnell, G.S. Salvesen, J. Travis, J.C. Whisstock, The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature, J. Biol. Chem. 276 (2001) 33293-33296.
3. S. Caccia, S. Ricagno, M. Bolognesi, Molecular bases of neuroserpin function and pathology, Biomol. Concepts 1 (2010) 117-130.
4. B.D. Roussel, T.M. Newton, E. Malzer, N. Simecek, I. Haq, S.E. Thomas, M.L. Burr, P.J. Lehner, D.C. Crowther, S.J. Marciniak, D.A. Lomas, Sterol metabolism regulates neuroserpin polymer degradation in the absence of the unfolded protein response in the dementia FENIB, Hum. Mol. Genet. 22 (2013) 4616-4626.
5. K.J. Kinghorn, D.C. Crowther, L.K. Sharp, C. Nerelius, R.L. Davis, H.T. Chang, C. Green, D.C. Gubb, J. Johansson, D.A. Lomas, Neuroserpin binds Aβ and is a neuroprotective component of amyloid plaques in Alzheimer disease, J. Biol. Chem. 281 (2006) 29268-29277.
6. R.L. Davis, A.E. Shrimpton, P.D. Holohan, C. Bradshaw, D. Feiglin, G.H. Collins, P. Sonderegger, J. Kinter, L.M. Becker, F. Lacbawan, D. Krasnewich, M. Muenke, D.A. Lawrence, M.S. Yerby, C.M. Shaw, B. Gooptu, P.R. Elliott, J.T. Finch, R.W. Carrell, D.A. Lomas, Familial dementia caused by polymerization of mutant neuroserpin, Nature 401 (1999) 376-379.
7. D. Belorgey, D.C. Crowther, R. Mahadeva, D.A. Lomas, Mutant neuroserpin (Ser49Pro) that causes the familial dementia FENIB is a poor proteinase inhibitor and readily forms polymers in vitro, J. Biol. Chem. 277 (2002) 17367-17373.
8. D. Belorgey, L.K. Sharp, D.C. Crowther, M. Onda, J. Johansson, D.A. Lomas, Neuroserpin Portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymers: implications for the epilepsy seen in the dementia FENIB, Eur. J. Biochem. 71 (2004) 3360-3367.
9. M. Onda, D. Belorgey, L.K. Sharp, D.A. Lomas, Latent S49P neuroserpin forms polymers in the dementia familial encephalopathy with neuroserpin inclusion bodies, J. Biol. Chem. 280 (2005) 13735-13741.
10. E. Miranda, K. Romisch, D.A. Lomas, Mutants of neuroserpin that cause dementia accumulate as polymers within the endoplasmic reticulum, J. Biol. Chem. 279 (2004) 28283-28291.
11. E. Miranda, I. MacLeod, M.J. Davies, J. Perez, K. Romisch, D.C. Crowther, D.A. Lomas, The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB, Hum. Mol. Genet. 17 (2008) 1527-1539.
12. R.W. Carrell, D.A. Lomas, Conformational disease, Lancet 350 (1997) 134-138.
13. P.G. Gettins, Serpin structure, mechanism, and function, Chem. Rev. 102 (2002) 4751-4804.
14. J.A. Huntington, R.J. Read, R.W. Carrell, Structure of a serpin-protease complex shows inhibition by deformation, Nature 407 (2007) 923-926.
15. S. Ricagno, S. Caccia, G. Sorrentino, G. Antonini, M. Bolognesi, Human neuroserpin: structure and time-dependent inhibition, J. Mol. Biol. 388 (2009) 109-121.
16. J.C. Whisstock, S.P. Bottomley, Molecular gymnastics: serpin structure, folding and misfolding, Curr. Opin. Struct. Biol. 16 (2006) 761-768.
17. U.I. Ekeowa, J. Freeke, E. Miranda, B. Gooptu, M.F. Bush, J. Perez, J. Teckman, C.V. Robinson, D.A. Lomas, Defining the mechanism of polymerization in the serpinopathies, Proc. Natl. Acad. Sci. U. S. A. 107 (2010) 17146-17151.
18. D.A. Lomas, D.L. Evans, J.T. Finch, R.W. Carrell, The mechanism of Z alpha 1-antitrypsin accumulation in the liver, Nature 357 (1992) 605-607.
19. 1-antitrypsin polymers are formed by reactive loop-β-sheet A linkage, J. Biol. Chem. 275 (2000) 33663-33668.
20. M. Yamasaki, W. Li, D.J. Johnson, J.A. Huntington, Crystal structure of a stable dimer reveals themolecular basis of serpin polymerization, Nature 455 (2008) 1255-1258.
21. M. Yamasaki, T.J. Sendall, M.C. Pearce, J.C. Whisstock, J.A. Huntington, Molecular basis of alpha1-antitrypsin defi ciency revealed by the structure of a domain-swapped trimer, EMBO Rep. 12 (2011) 1011-1017.
22. S. Ricagno, M. Pezzullo, A. Barbiroli, M. Manno, M. Levantino, M.G. Santangelo, F. Bonomi, M. Bolognesi, Two latent and two hyperstable polymeric forms of human neuroserpin, Biophys. J. 99 (2010) 3402-3411.
23. M.G. Santangelo, R. Noto, M. Levantino, A. Cupane, S. Ricagno, M. Pezzullo, M. Bolognesi, M.R. Mangione, V. Martorana, M. Manno, On the molecular structure of human neuroserpin polymers, Proteins 80 (2012) 8-13.
24. D. Belorgey, P. Hagglof, M. Onda, D.A. Lomas, pH dependent stability of neuroserpin ismediated by histidines 119 and 138; implications for the control of β-sheet A and polymerization, Methods 53 (2010) 255-266.
25. R. Noto, M.G. Santangelo, S. Ricagno, M.R. Mangione, M. Levantino, M. Pezzullo, V. Martorana, A. Cupane, M. Bolognesi, M. Manno, The tempered polymerization of human neuroserpin, PLoS One 7 (2012) e32444.
26. A. Chiou, P. Hagglof, A. Orte, A.Y. Chen, P.D. Dunne, D. Belorgey, S. Karlsson-Li, D.A. Lomas, D. Klenerman, Probing neuroserpin polymerization and interaction with amyloid-β peptides using single molecule fluorescence, Biophys. J. 97 (2009) 2306-2315.
27. 1-antitrypsin, J. Biol. Chem. 274 (1999) 9548-9555.
28. S. Takehara, M. Onda, J. Zhang, M. Nishiyama, X. Yang, B. Mikami, D.A. Lomas, The 2. 1-A˚ crystal structure of native neuroserpin reveals unique structural elements that contribute to conformational instability, J. Mol. Biol. 388 (2009) 11-20.
29. B. Gooptu, D.A. Lomas, Conformational pathology of the serpins: themes, variations and therapeutic strategies, Annu. Rev. Biochem. 78 (2009) 147-176.
30. H. Im, M.S. Woo, K.Y. Hwang, M.H. Yu, Interactions causing the kinetic trap in serpin protein folding, J. Biol. Chem. 277 (2002) 46347-46354.
31. Q. Zhang, A.M. Buckle, R.H. Law, M.C. Pearce, L.D. Cabrita, G.J. Lloyd, J.A. Irving, A.I. Smith, K. Ruzyla, J. Rossjohn, S.P. Bottomley, J.C. Whisstock, The N terminus of the serpin, tengpin, functions to trap the metastable native state, EMBO Rep. 8 (2007) 658-663.
32. L. Beinrohr, V. Harmat, J. Dobo, Z. Lorincz, P. Gal, P. Zavodszky, C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease, J. Biol. Chem. 282 (2007) 21100-21109.
33. T.J. Stout, H. Graham, D.I. Buckley, D.J. Matthews, Structures of active and latent PAI-1: a possible stabilizing role for chloride ions, Biochemistry 39 (2000) 8460-8469.
34. 1-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease, Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 67-72.
35. S. Takehara, J. Zhang, X. Yang, N. Takahashi, B. Mikami, M. Onda, Refolding and polymerization pathways of neuroserpin, J. Mol. Biol. 403 (2010) 751-762.
36. A. Sarkar, C. Zhou, R. Meklemburg, P. Wintrode, Local conformational flexibility provides a basis for facile polymer formation in human neuroserpin, Biophys. J. 101 (2011) 1758-1765.
37. D. Belorgey, J.A. Irving, U.I. Ekeowa, J. Freeke, B.D. Rouseel, E. Miranda, J. Pérez, C.V. Robinson, S.J. Marciniak, D.C. Crowther, C.H. Michel, D.A. Lomas, Characterization of serpin polymers in vitro and in vivo, Methods 53 (2011) 255-266.
38. S.M. Kelly, T.J. Jess, N.C. Price, How to study proteins by circular dichroism, Biophys. Biochem. Acta 1751 (2005) 119-139.
39. J.R. Lakowicz, Principles of Fluorescence Spectroscopy, Kluwer Academic/Plenum Publishers, New York, 1999.
40. J.A. Gardecki, M. Maroncelli, Set of secondary emission standards for calibration of the spectral responsivity inemission spectroscopy, Appl. Spectrosc. 52 (1998) 1179-1189.
41. A.D.MacKerell Jr., D. Bashford, M. Bellott, R.L. Dunbrack Jr., J.D. Evanseck, M.J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F.T.K. Lau, C. Mattos, S. Michnick, T. Ngo, D.T. Nguyen, B. Prodhom, W.E. Reiher III, B. Roux, M. Schlenkrich, J.C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiorkiewicz-Kuczera, D. Yin, M. Karplus, All-atom empirical potential for molecular modeling and dynamics studies of proteins, J. Phys. Chem. B 102 (1998) 3586-3616.
42. J.C. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R.D. Skeel, L. Kalé, K. Schulten, Scalable molecular dynamics with NAMD, J. Comput. Chem. 26 (2005) 1781-1802.
43. N. Sreerama, R.W. Woody, Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set, Anal. Biochem. 287 (2000) 252-260.
44. Y.K. Reshetnyak, E.A. Burstein, Decomposition of protein tryptophan fluorescence spectra into log-normal components. II. The statistical proof of discreteness of tryptophan classes in proteins, Biophys. J. 81 (2001) 1710-1734.
45. J.L. Meagher, J.M. Beechem, S.T. Olson, P.G.W. Gettins, Deconvolution of the fluorescence emission spectrum of human antithrombin and identification of the tryptophan residues that are responsive to heparin binding, J. Biol. Chem. 273 (1998) 23283-23289.
46. D.J. Tew, S.P. Bottomley, Probing the equilibrium denaturation of the serpin a1-antitrypsin with single tryptophan mutants; evidence for structure in the urea unfolded state, J. Mol. Biol. 313 (2001) 1161-1169.
47. M.C. Pearce, L.D. Cabrita, A.M. Ellisdon, S.P. Bottomley, The loss of tryptophan 194 in antichymotrypsin lowers the kinetic barrier to misfolding, FEBS J. 274 (2007) 3622-3632.
48. J. Eisinger, B. Feuer, A.A. Lamola, Intramolecular singlet excitation transfer. Applications to polypeptides, Biochemistry 8 (1969) 3908-3915.
49. P.R. Elliott, X.Y. Pei, T.R. Dafforn, D.A. Lomas, Topography of a 2.0 A˚ structure of α1-antitrypsin reveals targets for rational drug design to prevent conformational disease, Protein Sci. 9 (2000) 1274-1281.
50. M.A. Dunstone, W. Dai, J.C. Whisstock, J. Rossjohn, R.N. Pike, et al., Cleaved antitrypsin polymers at atomic resolution, Protein Sci. 9 (2000) 417-420.
51. D. Frishman, P. Argos, Knowledge-based protein secondary structure assignment, Proteins Struct. Funct. Genet. 23 (1995) 566-579.
52. A.G. Gvritishvili, A.V. Gribenko, G.I. Makhatadze, Cooperativity of complex salt bridges, Protein Sci. 17 (2008) 1285-1290.
53. J.A. Irving, R.N. Pike, A.M. Lesk, J.C. Whisstock, Phylogen of the serpin superfamily: implications of patterns of amino acid conservation for structure and function, Genom. Res. 10 (2000) 1845-1864.
54. H.J. Berendsen, S. Hayward, Collective protein dynamics in relation to function, Curr. Opin. Struct. Biol. 10 (2000) 165-169.
55. Z.P. Weng, C. Delisi, S. Vajda, Empirical free energy calculation: comparison to calorimetric data, Protein Sci. 6 (1997) 1976-1984.
56. G.D. Rose, R. Wolfenden, Hydrogen bonding, hydrophobicity, packing, and protein folding, Annu. Rev. Biophys. Biomol. Struct. 22 (1993) 381-415.
57. D. Shortle, Denatured states of proteins and their roles in folding and stability, Curr. Opin. Struct. Biol. 3 (1993) 66-74.
58. S. Kumar, R. Nussinov, Close-range electrostatics interactions in proteins, Chembiochem 3 (2002) 604-617.
59. S.D. Pickett, M.J. Sternberg, Empirical scale of side-chain conformational entropy in protein folding, J. Mol. Biol. 231 (1993) 825-839.
60. T.R. Dafforn, R.N. Pike, S.P. Bottomley, Physical characterization of serpin conformers, Methods 32 (2004) 150-158.
61. Y. Tsutsui, A. Sarkar, P.L. Wintrode, Probing serpin conformational change using mass spectrometry and related methods, Methods Enzymol. 501 (2011) 325-350.
62. R. Carrotta, M. Manno, D. Bulone, V. Martorana, P.L. San Biagio, Protofibril formation of amyloid b-protein at low pH via a non-cooperative elongation mechanism, J. Biol. Chem. 280 (2005) 30001-30008.