High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndrome

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 31, 2015, Pages 9620-9625

  Casina, Veronica C ^a   Hu, Wenbing ^a   Mao, Jian Hua ^a   Lu, Rui Nan ^a   Hanby, Hayley A ^a   Pickens, Brandy ^a   Kan, Zhong Yuan ^a   Lim, Woon K ^b   Mayne, Leland ^a   Ostertag, Eric M ^a   Kacir, Stephen ^a   Siegel, Don L ^a   Englander, S Walter ^a   Zheng, X Long ^a,c  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b Pusan National University   (South Korea)

^c University of Alabama at Birmingham   (United States)

Author keywords

ADAMTS13; Autoimmunity; Hydrogen exchange; Thrombotic thrombocytopenic purpura; Von willebrand factor

Indexed keywords

IMMUNOGLOBULIN G ANTIBODY; PEPTIDE FRAGMENT; VON WILLEBRAND FACTOR; VON WILLEBRAND FACTOR CLEAVING PROTEINASE; ADAM PROTEIN; ADAMTS13 PROTEIN, HUMAN; ANTIGEN; EPITOPE; IMMUNOGLOBULIN G; PROTEIN BINDING; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY;

AFFINITY CHROMATOGRAPHY; ANIMAL CELL; ANTIBODY COMBINING SITE; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; CLINICAL ARTICLE; COMPLEMENTARITY DETERMINING REGION; CONTROLLED STUDY; DEUTERIUM HYDROGEN EXCHANGE; EPITOPE MAPPING; HUMAN; IMMUNOPRECIPITATION; MASS SPECTROMETRY; MOLECULAR WEIGHT; NONHUMAN; PHAGE DISPLAY; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEINASE INHIBITION; THROMBOTIC THROMBOCYTOPENIC PURPURA; WESTERN BLOTTING; ADULT; AGED; AMINO ACID SEQUENCE; BINDING COMPETITION; BINDING SITE; BLOOD; CHEMISTRY; CHILD; DEMOGRAPHY; FEMALE; GENE DELETION; KINETICS; MALE; METABOLISM; MIDDLE AGED; MOLECULAR GENETICS; PATHOLOGY; PROCEDURES; PURPURA, THROMBOTIC THROMBOCYTOPENIC; SEQUENCE ALIGNMENT; YOUNG ADULT;

ADAM PROTEINS; ADULT; AGED; AMINO ACID SEQUENCE; ANTIGENS; BINDING SITES; BINDING, COMPETITIVE; CHILD; DEMOGRAPHY; DEUTERIUM EXCHANGE MEASUREMENT; EPITOPE MAPPING; EPITOPES; FEMALE; HUMANS; IMMUNOGLOBULIN G; KINETICS; MALE; MASS SPECTROMETRY; MIDDLE AGED; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEOLYSIS; PURPURA, THROMBOTIC THROMBOCYTOPENIC; SEQUENCE ALIGNMENT; SEQUENCE DELETION; SINGLE-CHAIN ANTIBODIES; YOUNG ADULT;

EID: 84938900181     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1512561112     Document Type: Article

References (46)

1. Moake JL (2002) Thrombotic thrombocytopenic purpura: The systemic clumping "plague." Annu Rev Med 53:75-88.
2. Bell WR, Braine HG, Ness PM, Kickler TS (1991) Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 325(6):398-403.
3. Tsai HM, Lian EC (1998) Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 339(22):1585-1594.
4. Zheng XL, et al. (2010) Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura. Haematologica 95(9):1555-1562.
5. Furlan M, et al. (1998) von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 339(22): 1578-1584.
6. Klaus C, et al. (2004) Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. Blood 103(12):4514-4519.
7. Pos W, et al. (2009) VH1-69 germline encoded antibodies directed towards ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 7(3):421-428.
8. Pos W, et al. (2011) Residues Arg568 and Phe592 contribute to an antigenic surface for anti-ADAMTS13 antibodies in the spacer domain. Haematologica 96(11): 1670-1677.
9. Jian C, et al. (2012) Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Blood 119(16):3836-3843.
10. Luken BM, et al. (2006) Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP. Thromb Haemost 96(3):295-301.
11. Luken BM, et al. (2005) The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 93(2):267-274.
12. Chen Y, et al. (1999) Selection and analysis of an optimized anti-VEGF antibody: Crystal structure of an affinity-matured Fab in complex with antigen. J Mol Biol 293(4):865-881.
13. Beyer BM, et al. (2008) Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody. J Mol Biol 382(4):942-955.
14. Schaller M, Vogel M, Kentouche K, Lämmle B, Kremer Hovinga JA (2014) The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs. Blood 124(23):3469-3479.
15. Brock A (2012) Fragmentation hydrogen exchange mass spectrometry: A review of methodology and applications. Protein Expr Purif 84(1):19-37.
16. Coales SJ, Tuske SJ, Tomasso JC, Hamuro Y (2009) Epitope mapping by amide hydrogen/deuterium exchange coupled with immobilization of antibody, on-line proteolysis, liquid chromatography and mass spectrometry. Rapid Commun Mass Spectrom 23(5):639-647.
17. Pandit D, et al. (2012) Mapping of discontinuous conformational epitopes by amide hydrogen/deuterium exchange mass spectrometry and computational docking. J Mol Recognit 25(3):114-124.
18. Houde D, Engen JR (2013) Conformational analysis of recombinant monoclonal antibodies with hydrogen/deuterium exchange mass spectrometry. Methods Mol Biol 988:269-289.
19. Zhang Q, et al. (2011) Epitope mapping of a 95 kDa antigen in complex with antibody by solution-phase amide backbone hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem 83(18): 7129-7136.
20. Kan ZY, Walters BT, Mayne L, Englander SW (2013) Protein hydrogen exchange at residue resolution by proteolytic fragmentation mass spectrometry analysis. Proc Natl Acad Sci USA 110(41):16438-16443.
21. Kan ZY, Mayne L, Chetty PS, Englander SW (2011) ExMS: Data analysis for HX-MS experiments. J Am Soc Mass Spectrom 22(11):1906-1915.
22. Mayne L, et al. (2011) Many overlapping peptides for protein hydrogen exchange experiments by the fragment separation-mass spectrometry method. J Am Soc Mass Spectrom 22(11):1898-1905.
23. Walters BT, Ricciuti A, Mayne L, Englander SW (2012) Minimizing back exchange in the hydrogen exchange-mass spectrometry experiment. J Am Soc Mass Spectrom 23(12):2132-2139.
24. Zhang L, et al. (2006) Creation of a recombinant peptide substrate for fluorescence resonance energy transfer-based protease assays. Anal Biochem 358(2):298-300.
25. Raife TJ, et al. (2009) Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage site. Blood 114(8):1666-1674.
26. Furlan M, Robles R, Lämmle B (1996) Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 87(10):4223-4234.
27. Ai J, Smith P, Wang S, Zhang P, Zheng XL (2005) The proximal carboxyl-terminal domains of ADAMTS13 determine substrate specificity and are all required for cleavage of von Willebrand factor. J Biol Chem 280(33):29428-29434.
28. Bao J, Xiao J, Mao Y, Zheng XL (2014) Carboxyl terminus of ADAMTS13 directly inhibits platelet aggregation and ultra large von Willebrand factor string formation under flow in a free-thiol-dependent manner. Arterioscler Thromb Vasc Biol 34(2): 397-407.
29. Han Y, Xiao J, Falls E, Zheng XL (2011) A shear-based assay for assessing plasma ADAMTS13 activity and inhibitors in patients with thrombotic thrombocytopenic purpura. Transfusion 51(7):1580-1591.
30. Jin SY, et al. (2013) AAV-mediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpura. Blood 121(19):3825-3829, S3821-S3823.
31. Gao W, Anderson PJ, Majerus EM, Tuley EA, Sadler JE (2006) Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease. Proc Natl Acad Sci USA 103(50):19099-19104.
32. Gao W, Anderson PJ, Sadler JE (2008) Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity. Blood 112(5):1713-1719.
33. Zheng X, et al. (2001) Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem 276(44):41059-41063.
34. Sorvillo N, et al. (2014) Identification of N-linked glycosylation and putative O-fucosylation, C-mannosylation sites in plasma derived ADAMTS13. J Thromb Haemost 12(5):670-679.
35. Pos W, et al. (2010) An autoantibody epitope comprising residues R660, Y661, and Y665 in the ADAMTS13 spacer domain identifies a binding site for the A2 domain of VWF. Blood 115(8):1640-1649.
36. Jin SY, Skipwith CG, Zheng XL (2010) Amino acid residues Arg(659), Arg(660), and Tyr (661) in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor. Blood 115(11):2300-2310.
37. Englander SW, Hiller R (2001) Dynamics and thermodynamics of hyperthermophilic proteins by hydrogen exchange. Methods Enzymol 334:342-350.
38. Englander SW, Sosnick TR, Englander JJ, Mayne L (1996) Mechanisms and uses of hydrogen exchange. Curr Opin Struct Biol 6(1):18-23.
39. Bai Y, Milne JS, Mayne L, Englander SW (1993) Primary structure effects on peptide group hydrogen exchange. Proteins 17(1):75-86.
40. Connelly GP, Bai Y, Jeng MF, Englander SW (1993) Isotope effects in peptide group hydrogen exchange. Proteins 17(1):87-92.
41. Skinner JJ, Lim WK, Bedard S, Black BE, Englander SW (2012) Protein hydrogen exchange: Testing current models. Protein Sci 21(7):987-995.
42. Skinner JJ, Lim WK, Bedard S, Black BE, Englander SW (2012) Protein dynamics viewed by hydrogen exchange. Protein Sci 21(7):996-1005.
43. Paterson Y, Englander SW, Roder H (1990) An antibody binding site on cytochrome c defined by hydrogen exchange and two-dimensional NMR. Science 249(4970): 755-759.
44. Williams DC, Jr, Rule GS, Poljak RJ, Benjamin DC (1997) Reduction in the amide hydrogen exchange rates of an anti-lysozyme Fv fragment due to formation of the Fv-lysozyme complex. J Mol Biol 270(5):751-762.
45. Hu W, et al. (2013) Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry. Proc Natl Acad Sci USA 110(19):7684-7689.
46. Payne AS, et al. (2005) Genetic and functional characterization of human pemphigus vulgaris monoclonal autoantibodies isolated by phage display. J Clin Invest 115(4): 888-899.