Hydrogen/Deuterium Exchange Mass Spectrometry:Potential for Investigating Innate Immunity Proteins

  • Michael C. Schuster
  • Hui Chen
  • John D. Lambris
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 598)


Ligand Binding Domain Nuclear Magnetic Resonance Spectroscopy Protective Antigen Full Agonist Lethal Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alsenz, J., Becherer, J.D., Nilsson, B. and Lambris, J.D. (1990). Structural and Functional-Analysis of C3 Using Monoclonal-Antibodies. Current Topics in Microbiology and Immunology, 153, 235-248.PubMedGoogle Scholar
  2. Arold, S., Franken, P., Strub, M.P., Hoh, F., Benichou, S., Benarous, R. and Dumas, C. (1997). The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling. Structure, 5(10), 1361-1372.PubMedCrossRefGoogle Scholar
  3. Arold, S.T. and Bauer, A.S. (2001). Dynamic Nef and Nef dynamics: how structure could explain the complex activities of this small HIV protein. Trends in Biochemical Sciences, 26(6), 356–363.PubMedCrossRefGoogle Scholar
  4. Becherer, J.D., Alsenz, J. and Lambris, J.D. (1990). Molecular Aspects of C3 Interactions and Structural Functional-Analysis of C3 from Different Species. Current Topics in Microbiology and Immunology, 153, 45–72.PubMedGoogle Scholar
  5. Berger, J.P., Petro, A.E., Macnaul, K.L., Kelly, L.J., Zhang, B.B., Richards, K., Elbrecht, A., Johnson, B.A., Zhou, G.C., Doebber, T.W., Biswas, C., Parikh, M., Sharma, N., Tanen, M.R., Thompson, G.M., Ventre, J., Adams, A.D., Mosley, R., Surwit, R.S. and Moller, D.E. (2003). Distinct properties and advantages of a novel peroxisome proliferator-activated protein gamma selective modulator. Molecular Endocrinology, 17(4), 662–676.PubMedCrossRefGoogle Scholar
  6. Bradley, K.A., Mogridge, J., Mourez, M., Collier, R.J. and Young, J.A.T. (2001). Identification of the cellular receptor for anthrax toxin. Nature, 414(6860), 225–229.PubMedCrossRefGoogle Scholar
  7. Brown, K.K., Henke, B.R., Blanchard, S.G., Cobb, J.E., Mook, R., Kaldor, I., Kliewer, S.A., Lehmann, J.M., Lenhard, J.M., Harrington, W.W., Novak, P.J., Faison, W., Binz, J.G., Hashim, M.A., Oliver, W.O., Brown, H.R., Parks, D.J., Plunket, K.D., Tong, W.Q., Menius, J.A., Adkison, K., Noble, S.A. and Willson, T.M. (1999). A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes, 48(7), 1415–1424.PubMedCrossRefGoogle Scholar
  8. Busenlehner, L.S. and Armstrong, R.N. (2005). Insights into enzyme structure and dynamics elucidated by amide H/D exchange mass spectrometry. Archives of Biochemistry and Biophysics, 433(1), 34-46.PubMedCrossRefGoogle Scholar
  9. Carroll, M.C. and Holers, V.M. (2005). Innate autoimmunity. Advances in Immunology, 86, 137-157.Google Scholar
  10. Cravello, L., Lascoux, D. and Forest, E. (2003). Use of different proteases working in acidic conditions to improve sequence coverage and resolution in hydrogen/deuterium exchange of large proteins. Rapid Communications in Mass Spectrometry, 17(21), 2387-2393.PubMedCrossRefGoogle Scholar
  11. Cunningham, K., Lacy, D.B., Mogridge, J. and Collier, R.J. (2002). Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen. Proceedings of the National Academy of Sciences of the United States of America, 99(10), 7049-7053.PubMedCrossRefGoogle Scholar
  12. Domon, B. and Aebersold, R. (2006). Review - Mass spectrometry and protein analysis. Science, 312(5771), 212-217.PubMedCrossRefGoogle Scholar
  13. Elliott, J.L., Mogridge, J. and Collier, R.J. (2000). A quantitative study of the interactions of Bacillus anthracis edema factor and lethal factor with activated protective antigen. Biochemistry, 39(22), 6706-6713.PubMedCrossRefGoogle Scholar
  14. Englander, S.W. and Kallenbach, N.R. (1983). Hydrogen-Exchange and Structural Dynamics of Proteins and Nucleic-Acids. Quarterly Reviews of Biophysics, 16(4), 521-655.PubMedGoogle Scholar
  15. Englander, S.W., Mayne, L., Bai, Y. and Sosnick, T.R. (1997). Hydrogen exchange: The modern legacy of Linderstrom-Lang. Protein Science, 6(5), 1101-1109.PubMedGoogle Scholar
  16. Eyles, S.J. and Kaltashov, I.A. (2004). Methods to study protein dynamics and folding by mass spectrometry. Methods, 34(1), 88-99.PubMedCrossRefGoogle Scholar
  17. Fishelson, Z., Pangburn, M.K. and Mullereberhard, H.J. (1984). Characterization of the Initial C-3 Convertase of the Alternative Pathway of Human-Complement. Journal of Immunology, 132(3), 1430-1434.Google Scholar
  18. Gampe, R.T., Montana, V.G., Lambert, M.H., Miller, A.B., Bledsoe, R.K., Milburn, M.V., Kliewer, S.A., Willson, T.M. and Xu, H.E. (2000). Asymmetry in the PPAR gamma/RXR alpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Molecular Cell, 5(3), 545-555.PubMedCrossRefGoogle Scholar
  19. Geyer, M., Fackler, O.T. and Peterlin, B.M. (2001). Structure-function relationships in HIV-1 Nef. Embo Reports, 2(7), 580-585.PubMedCrossRefGoogle Scholar
  20. Grzesiek, S., Bax, A., Clore, G.M., Gronenborn, A.M., Hu, J.S., Kaufman, J., Palmer, I., Stahl, S.J. and Wingfield, P.T. (1996). The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase. Nature Structural Biology, 3(4), 340-345.PubMedCrossRefGoogle Scholar
  21. Grzesiek, S., Bax, A., Hu, J.S., Kaufman, J., Palmer, I., Stahl, S.J., Tjandra, N. and Wingfield, P.T. (1997). Refined solution structure and backbone dynamics of HIV-1 Nef. Protein Science, 6(6), 1248-1263.PubMedCrossRefGoogle Scholar
  22. Hamuro, Y., Coales, S.J., Morrow, J.A., Molnar, K.S., Tuske, S.J., Southern, M.R. and Griffin, P.R. (2006). Hydrogen/deuterium-exchange (H/D-Ex) of PPAR gamma LBD in the presence of various modulators. Protein Science, 15(8), 1883-1892.PubMedCrossRefGoogle Scholar
  23. Hochrein, J.M., Wales, T.E., Lerner, E.C., Schiavone, A.P., Smithgall, T.E. and Engen, J.R. (2006). Conformational features of the full-length HIV and SIV Nef proteins determined by mass spectrometry. Biochemistry, 45(25), 7733-7739.PubMedCrossRefGoogle Scholar
  24. Hoofnagle, A.N., Resing, K.A. and Ahn, N.G. (2003). Protein analysis by hydrogen exchange mass spectrometry. Annual Review of Biophysics and Biomolecular Structure, 32, 1-25.Google Scholar
  25. Janssen, B.J.C., Huizinga, E.G., Raaijmakers, H.C.A., Roos, A., Daha, M.R., Nilsson-Ekdahl, K., Nilsson, B. and Gros, P. (2005). Structures of complement component C3 provide insights into the function and evolution of immunity. Nature, 437(7058), 505-511.PubMedCrossRefGoogle Scholar
  26. Kallenberger, B.C., Love, J.D., Chatterjee, V.K.K. and Schwabe, J.W.R. (2003). A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease. Nature Structural Biology, 10(2), 136-140.PubMedCrossRefGoogle Scholar
  27. Kenzel, S. and Henneke, P. (2006). The innate immune system and its relevance to neonatal sepsis. Current Opinion in Infectious Diseases, 19(3), 264-270.PubMedCrossRefGoogle Scholar
  28. Lacy, D.B., Mourez, M., Fouassier, A. and Collier, R.J. (2002). Mapping the anthrax protective antigen binding site on the lethal and edema factors. Journal of Biological Chemistry, 277(4), 3006-3010.PubMedCrossRefGoogle Scholar
  29. Lambris, J.D. (1988). The Multifunctional Role of C-3, the 3rd Component of Complement. Immunology Today, 9(12), 387-393.PubMedCrossRefGoogle Scholar
  30. Lanman, J. and Prevelige, P.E. (2004). High-sensitivity mass spectrometry for imaging subunit interactions: hydrogen/deuterium exchange. Current Opinion in Structural Biology, 14(2), 181-188.PubMedCrossRefGoogle Scholar
  31. Lee, C.H., Saksela, K., Mirza, U.A., Chait, B.T. and Kuriyan, J. (1996). Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain. Cell, 85(6), 931-942.PubMedCrossRefGoogle Scholar
  32. Leesnitzer, L.M., Parks, D.J., Bledsoe, R.K., Cobb, J.E., Collins, J.L., Consler, T.G., Davis, R.G., Hull-Ryde, E.A., Lenhard, J.M., Patel, L., Plunket, K.D., Shenk, J.L., Stimmel, J.B., Therapontos, C., Willson, T.M. and Blanchard, S.G. (2002). Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662. Biochemistry, 41(21), 6640-6650.PubMedCrossRefGoogle Scholar
  33. Melnyk, R.A., Hewitt, K.M., Lacy, D.B., Lin, H.C., Gessner, C.R., Li, S., Woods, V.L. and Collier, R.J. (2006). Structural determinants for the binding of anthrax lethal factor to oligomeric protective antigen. Journal of Biological Chemistry, 281(3), 1630-1635.PubMedCrossRefGoogle Scholar
  34. Molloy, S.S., Bresnahan, P.A., Leppla, S.H., Klimpel, K.R. and Thomas, G. (1992). Human Furin Is a Calcium-Dependent Serine Endoprotease That Recognizes the Sequence Arg-X-X-Arg and Efficiently Cleaves Anthrax Toxin Protective Antigen. Journal of Biological Chemistry, 267(23), 16396-16402.PubMedGoogle Scholar
  35. Nagar, B., Jones, R.G., Diefenbach, R.J., Isenman, D.E. and Rini, J.M. (1998). X-ray crystal structure of C3d: A C3 fragment and ligand for complement receptor 2. Science, 280(5367), 1277-1281.PubMedCrossRefGoogle Scholar
  36. Oberfield, J.L., Collins, J.L., Holmes, C.P., Goreham, D.M., Cooper, J.P., Cobb, J.E., Lenhard, J.M., Hull-Ryde, E.A., Mohr, C.P., Blanchard, S.G., Parks, D.J., Moore, L.B., Lehmann, J.M., Plunket, K., Miller, A.B., Milburn, M.V., Kliewer, S.A. and Willson, T.M. (1999). A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation. Proceedings of the National Academy of Sciences of the United States of America, 96(11), 6102-6106.PubMedCrossRefGoogle Scholar
  37. Olefsky, J.M. and Saltiel, A.R. (2000). PPAR gamma and the treatment of insulin resistance. Trends in Endocrinology and Metabolism, 11(9), 362-368.PubMedCrossRefGoogle Scholar
  38. Renkema, G.H. and Saksela, K. (2000). Interactions of HIV-1 Nef with cellular signal transducing proteins. Frontiers in Bioscience, 5, D268-D283.Google Scholar
  39. Sahu, A. and Lambris, J.D. (2001). Structure and biology of complement protein C3, a connecting link between innate and acquired immunity. Immunological Reviews, 180, 35-48.Google Scholar
  40. Scobie, H.M., Rainey, G.J.A., Bradley, K.A. and Young, J.A.T. (2003). Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proceedings of the National Academy of Sciences of the United States of America, 100(9), 5170-5174.PubMedCrossRefGoogle Scholar
  41. Thurman, J.M. and Holers, V.M. (2006). The central role of the alternative complement pathway in human disease. Journal of Immunology, 176(3), 1305-1310.Google Scholar
  42. Wales, T.E. and Engen, J.R. (2006). Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrometry Reviews, 25(1), 158-170.PubMedCrossRefGoogle Scholar
  43. Walport, M.J. (2001a). Advances in immunology: Complement (First of two parts). New England Journal of Medicine, 344(14), 1058-1066.Google Scholar
  44. Walport, M.J. (2001b). Advances in immunology: Complement (Second of two parts). New England Journal of Medicine, 344(15), 1140-1144.Google Scholar
  45. Winters, M.S., Spellman, D.S. and Lambris, J.D. (2005). Solvent accessibility of native and hydrolyzed human complement protein 3 analyzed by hydrogen/deuterium exchange and mass spectrometry. Journal of Immunology, 174(6), 3469-3474.Google Scholar
  46. Xu, Y., Narayana, S.V. and Volanakis, J.E. (2001). Structural biology of the alternative pathway convertase. Immunological Reviews, 180, 123-135.PubMedCrossRefGoogle Scholar
  47. Yang, W., Rachez, C. and Freedman, L.P. (2000). Discrete roles for peroxisome proliferator-activated receptor gamma and retinoid X receptor in recruiting nuclear receptor coactivators. Molecular and Cellular Biology, 20(21), 8008-8017.PubMedCrossRefGoogle Scholar
  48. Zhang, S., Finkelstein, A. and Collier, R.J. (2004). Evidence that translocation of anthrax toxin’s lethal factor is initiated by entry of its N terminus into the protective antigen channel. Proceedings of the National Academy of Sciences of the United States of America, 101(48), 16756-16761.PubMedCrossRefGoogle Scholar
  49. Zhang, Z.Q. and Smith, D.L. (1993). Determination of Amide Hydrogen-Exchange by Mass-Spectrometry - a New Tool for Protein-Structure Elucidation. Protein Science, 2(4), 522-531.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Michael C. Schuster
    • 1
  • Hui Chen
    • 2
  • John D. Lambris
    • 3
  1. 1.Department of Medicine, Division of RheumatologyUniversity of PennsylvaniaPhiladelphia
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphia
  3. 3.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphia

Personalised recommendations