Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight

Scientific Reports

Volumn 8, Issue 1, 2018, Pages

  Caccia, Sonia ^a   Suffritti, Chiara ^a   Carzaniga, Thomas ^a   Berardelli, Romina ^b   Berra, Silvia ^a   Martorana, Vincenzo ^c   Fra, Annamaria ^b   Drouet, Christian ^d   Cicardi, Marco ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY OF BRESCIA   (Italy)

^c CNR   (Italy)

^d UNIV GRENOBLE ALPES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT COMPONENT C1S INHIBITOR;

ANGIONEUROTIC EDEMA; CASE REPORT; DEFICIENCY; FEMALE; GENETICS; HEREDITY; HUMAN; MIDDLE AGED; MUTATION;

ANGIOEDEMA; COMPLEMENT C1 INACTIVATOR PROTEINS; FEMALE; HEREDITY; HUMANS; MIDDLE AGED; MUTATION;

EID: 85041619709     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-017-16667-w     Document Type: Article

References (72)

1. Davis, A. E., Lu, F. & Mejia, P. C1 inhibitor, a multi-functional serine protease inhibitor. Thromb. Haemost. 104, 886-893 (2010).
2. Zuraw, B. L. & Christiansen, S. C. HAE Pathophysiology and Underlying Mechanisms. Clin. Rev. Allergy Immunol. 51, 216-229 (2016).
3. Hofman, Z. L. M., Relan, A. & Hack, C. E. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites. Clin. Rev. Allergy Immunol. 50, 34-40 (2014).
4. Longhurst, H. & Cicardi, M. Hereditary angio-oedema. Lancet Lond. Engl. 379, 474-481 (2012).
5. Kalmár, L., Hegedüs, T., Farkas, H., Nagy, M. & Tordai, A. HAEdb: a novel interactive, locus-specific mutation database for the C1 inhibitor gene. Hum. Mutat. 25, 1-5 (2005).
6. López-Lera, A., Garrido, S., Roche, O. & López-Trascasa, M. SERPING1 mutations in 59 families with hereditary angioedema. Mol. Immunol. 49, 18-27 (2011).
7. Pappalardo, E., Zingale, L. C. & Cicardi, M. Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with Danazol. Immunol. Lett. 86, 271-276 (2003).
8. Gösswein, T. et al. Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenet. Genome Res. 121, 181-188 (2008).
9. Rosen, F. S., Pensky, J., Donaldson, V. & Charache, P. Hereditary Angioneurotic Edema: Two Genetic Variants. Science 148, 957-958 (1965).
10. Parad, R. B., Kramer, J., Strunk, R. C., Rosen, F. S. & Davis, A. E. Dysfunctional C1 inhibitor Ta: deletion of Lys-251 results in acquisition of an N-glycosylation site. Proc. Natl. Acad. Sci. USA 87, 6786-6790 (1990).
11. Zuraw, B. L. Hereditary Angioedema. N. Engl. J. Med. 359, 1027-1036 (2008).
12. Blanch, A. et al. First case of homozygous C1 inhibitor deficiency. J. Allergy Clin. Immunol. 118, 1330-1335 (2006).
13. Büyüköztürk, S. et al. A Turkish family with a novel mutation in the promoter region of the C1 inhibitor gene. J. Allergy Clin. Immunol. 123, 962-964 (2009).
14. López-Lera, A. et al. A new case of homozygous C1-inhibitor deficiency suggests a role for Arg378 in the control of kinin pathway activation. J. Allergy Clin. Immunol. 126, 1307-1310.e3 (2010).
15. Verpy, E. et al. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema. Am. J. Hum. Genet. 59, 308-319 (1996).
16. Bafunno, V. et al. De novo homozygous mutation of the C1 inhibitor gene in a patient with hereditary angioedema. J. Allergy Clin. Immunol. 132, 748-750.e3 (2013).
17. Gettins, P. G. W. & Olson, S. T. Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance. Biochem. J. 473, 2273-2293 (2016).
18. Roussel, B. D. et al. Unravelling the twists and turns of the serpinopathies. FEBS J. 278, 3859-3867 (2011).
19. Whisstock, J. C. et al. Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions. J. Biol. Chem. 285, 24307-24312 (2010).
20. Lomas, D. A. et al. Molecular mousetraps and the serpinopathies. Biochem. Soc. Trans. 33, 321-330 (2005).
21. Aulak, K. S. et al. A hinge region mutation in C1-inhibitor (Ala436- Thr) results in nonsubstrate-like behavior and in polymerization of the molecule. J. Biol. Chem. 268, 18088-18094 (1993).
22. Eldering, E., Verpy, E., Roem, D., Meo, T. & Tosi, M. COOH-terminal substitutions in the serpin C1 inhibitor that cause loop overinsertion and subsequent multimerization. J. Biol. Chem. 270, 2579-2587 (1995).
23. Madsen, D. E. et al. Presence of C1-inhibitor polymers in a subset of patients suffering from hereditary angioedema. PloS One 9, e112051 (2014).
24. Verpy, E. et al. 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 (1995).
25. Irving, J. A., Pike, R. N., Lesk, A. M. & Whisstock, J. C. Phylogeny of the Serpin Superfamily: Implications of Patterns of Amino Acid Conservation for Structure and Function. Genome Res. 10, 1845-1864 (2000).
26. de Smet, B. J. et al. Clearance of human native, proteinase-complexed, and proteolytically inactivated C1-inhibitor in rats. Blood 81, 56-61 (1993).
27. Cugno, M. et al. Plasma levels of C1-inhibitor complexes and cleaved C1-inhibitor in patients with hereditary angioneurotic edema. J. Clin. Invest. 85, 1215-1220 (1990).
28. Vinci, G. et al. In vivo biosynthesis of endogenous and of human C1 inhibitor in transgenic mice: tissue distribution and colocalization of their expression. J. Immunol. Baltim. Md 1950 169, 5948-5954 (2002).
29. Fra, A. M. et al. Three New Alpha1-Antitrypsin Deficiency Variants Help to Define a C-Terminal Region Regulating Conformational Change and Polymerization. PLoS ONE 7 (2012).
30. Ghannam, A. et al. Contact system activation in patients with HAE and normal C1 inhibitor function. Immunol. Allergy Clin. North Am. 33, 513-533 (2013).
31. Ellis, R. J. Macromolecular crowding: an important but neglected aspect of the intracellular environment. Curr. Opin. Struct. Biol. 11, 114-119 (2001).
32. Minton, A. P. Influence of macromolecular crowding upon the stability and state of association of proteins: predictions and observations. J. Pharm. Sci. 94, 1668-1675 (2005).
33. Zimmerman, S. B. & Trach, S. O. Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli. J. Mol. Biol. 222, 599-620 (1991).
34. Zahedi, R., Aulak, K. S., Eldering, E. & Davis, A. E. Characterization of C1 inhibitor-Ta. A dysfunctional C1INH with deletion of lysine 251. J. Biol. Chem. 271, 24307-24312 (1996).
35. Huang, X. et al. Molecular Mechanism of Z ?1-Antitrypsin Deficiency. J. Biol. Chem. 291, 15674-15686 (2016).
36. Carrell, R. W. & Lomas, D. A. Conformational disease. Lancet Lond. Engl. 350, 134-138 (1997).
37. Fra, A. et al. Polymers of Z ?1-antitrypsin are secreted in cell models of disease. Eur. Respir. J. 47, 1005-1009 (2016).
38. Tan, L. et al. Circulating polymers in ?1-antitrypsin deficiency. Eur. Respir. J. 43, 1501-1504 (2014).
39. Miranda, E. et al. The pathological Trento variant of alpha-1-antitrypsin (E75V) shows nonclassical behaviour during polymerization. FEBS J. 284, 2110-2126 (2017).
40. Yamasaki, M., Sendall, T. J., Pearce, M. C., Whisstock, J. C. & Huntington, J. A. Molecular basis of ?1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep. 12, 1011-1017 (2011).
41. Madsen, D. E., Sidelmann, J. J., Biltoft, D., Gram, J. & Hansen, S. C1-inhibitor polymers activate the FXII-dependent kallikrein-kinin system: Implication for a role in hereditary angioedema. Biochim. Biophys. Acta 1850, 1336-1342 (2015).
42. Parmar, J. S. et al. Polymers of alpha(1)-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema. Am. J. Respir. Cell Mol. Biol. 26, 723-730 (2002).
43. Zimmerman, S. B. & Minton, A. P. Macromolecular crowding: biochemical, biophysical, and physiological consequences. Annu. Rev. Biophys. Biomol. Struct. 22, 27-65 (1993).
44. Speed, M. A., Wang, D. I. & King, J. Specific aggregation of partially folded polypeptide chains: the molecular basis of inclusion body composition. Nat. Biotechnol. 14, 1283-1287 (1996).
45. O'Reilly, M. S., Pirie-Shepherd, S., Lane, W. S. & Folkman, J. Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. Science 285, 1926-1928 (1999).
46. Corral, J. et al. Mutations in the shutter region of antithrombin result in formation of disulfide-linked dimers and severe venous thrombosis. J. Thromb. Haemost. 2, 931-939 (2004).
47. Fra, A., Yoboue, E. D. & Sitia, R. Cysteines as Redox Molecular Switches and Targets of Disease. Front. Mol. Neurosci. 10, 167 (2017).
48. Ronzoni, R. et al. Aberrant disulphide bonding contributes to the ER retention of alpha1-antitrypsin deficiency variants. Hum. Mol. Genet. 25, 642-650 (2016).
49. Konings, J. et al. Ongoing Contact Activation in Patients with Hereditary Angioedema. PLOS ONE 8, e74043 (2013).
50. Quastel, M., Harrison, R., Cicardi, M., Alper, C. A. & Rosen, F. S. Behavior in vivo of normal and dysfunctional C1 inhibitor in normal subjects and patients with hereditary angioneurotic edema. J. Clin. Invest. 71, 1041-1046 (1983).
51. Martínez-Martínez, I. et al. The Infective Polymerization of Conformationally Unstable Antithrombin Mutants May Play a Role in the Clinical Severity of Antithrombin Deficiency. Mol. Med. 18, 762-770 (2012).
52. Aguzzi, A. & Calella, A. M. Prions: protein aggregation and infectious diseases. Physiol. Rev. 89, 1105-1152 (2009).
53. Hofman, Z. L. M. et al. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process. J. Allergy Clin. Immunol. 138, 359-366 (2016).
54. Ghannam, A. et al. C1 inhibitor function using contact-phase proteases as target: evaluation of an innovative assay. Allergy 70, 1103-1111 (2015).
55. Reshef, A. et al. Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema attacks: a pilot study. Allergy 68, 118-124 (2013).
56. Nussberger, J., Cugno, M., Cicardi, M. & Agostoni, A. Local bradykinin generation in hereditary angioedema. J. Allergy Clin. Immunol. 104, 1321-1322 (1999).
57. Jaradat, S. A. et al. Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain. Mol. Immunol. 71, 123-130 (2016).
58. Nuijens, J. H., Huijbregts, C. C., van Mierlo, G. M. & Hack, C. E. Inactivation of C-1 inhibitor by proteases: demonstration by a monoclonal antibody of a neodeterminant on inactivated, non-complexed C-1 inhibitor. Immunology 61, 387-389 (1987).
59. Nuijens, J. H. et al. Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(-)-inhibitor complexes in sepsis. Blood 72, 1841-1848 (1988).
60. Monnier, N. et al. Characterisation of a new C1 inhibitor mutant in a patient with hepatocellular carcinoma. Mol. Immunol. 43, 2161-2168 (2006).
61. Bos, I. G. A. et al. Recombinant human C1-inhibitor produced in Pichia pastoris has the same inhibitory capacity as plasma C1-inhibitor. Biochim. Biophys. Acta 1648, 75-83 (2003).
62. Morrison, J. F. & Walsh, C. T. The behavior and significance of slow-binding enzyme inhibitors. Adv. Enzymol. Relat. Areas Mol. Biol. 61, 201-301 (1988).
63. Schechter, N. M. & Plotnick, M. I. Measurement of the kinetic parameters mediating protease-serpin inhibition. Methods San Diego Calif 32, 159-168 (2004).
64. Stein, P. E., Tewkesbury, D. A. & Carrell, R. W. Ovalbumin and angiotensinogen lack serpin S-R conformational change. Biochem. J. 262, 103-107 (1989).
65. van den Berg, B., Wain, R., Dobson, C. M. & Ellis, R. J. Macromolecular crowding perturbs protein refolding kinetics: implications for folding inside the cell. EMBO J. 19, 3870-3875 (2000).
66. Homchaudhuri, L., Sarma, N. & Swaminathan, R. Effect of crowding by dextrans and Ficolls on the rate of alkaline phosphatasecatalyzed hydrolysis: a size-dependent investigation. Biopolymers 83, 477-486 (2006).
67. Kuznetsova, I. M., Turoverov, K. K. & Uversky, V. N. What macromolecular crowding can do to a protein. Int. J. Mol. Sci. 15, 23090-23140 (2014).
68. Bos, I. G. A., Hack, C. E. & Abrahams, J. P. Structural and functional aspects of C1-inhibitor. Immunobiology 205, 518-533 (2002).
69. Lyskov, S. & Gray, J. J. The RosettaDock server for local protein-protein docking. Nucleic Acids Res. 36, W233-238 (2008).
70. Webb, B. & Sali, A. Comparative Protein Structure Modeling Using MODELLER. Curr. Protoc. Bioinforma. 54(5), 6.1-5.6.37 (2016).
71. Weinkam, P., Pons, J. & Sali, A. Structure-based model of allostery predicts coupling between distant sites. Proc. Natl. Acad. Sci. USA 109, 4875-4880 (2012).
72. Pettersen, E. F. et al. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612 (2004).