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Amyloid fibril formation by a domain of rat cell adhesion molecule

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Abstract

Amyloid fibrils are protein aggregates implicated in several amyloidotic diseases. Cellular membranes with local decrease in pH and dielectric constant are associated with the amyloid formation. In this study, domain 1 of cell adhesion molecule CD2 (CD2-1) is used for studying amyloid fibril formation in a water/trifluoroethanol (TFE) mixture. CD2-1 is an all β-sheet protein similar in topology to the amyloidogenic light chain variable domain, which deposits as amyloid in light chain amyloidosis at acidic pH. When incubated at pH 2.0 in the presence of 18% TFE, CD2-1 initiates the process to assemble into amyloid fibrils. It has been shown that TFE induces CD2-1 conformational change with a chemical transition (Cm) of 18% (v/v). ANS (1-anilinonapthalene-8-sulfonic acid) binding was used to show that the hydrophobic surface becomes exposed under these solvent conditions. Our studies indicate that partial formation of a non-native conformation and the exposure of the hydrophobic interior could be the origins of oligomerization and fibril formation of CD2-1.

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References

  1. Kirschner, D. A., Inouye, H., Duffy, L. K., Sinclair, A., Lind, M., and Selkoe, D. J. (1987) Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc. Natl. Acad. Sci. U. S. A. 84, 6953–6957.

    Article  PubMed  CAS  Google Scholar 

  2. Fraser, P. E., Duffy, L. K., O'Malley, M. B., Nguyen, J., Inouye, H., and Kirschner, D. A. (1991) Morphology and antibody recognition of synthetic beta-amyloid peptides. J. Neurosci. Res. 28, 474–485.

    Article  PubMed  CAS  Google Scholar 

  3. Kelly, J. W. (1998) The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr. Opin. Struct. Biol. 8, 101–106.

    Article  PubMed  CAS  Google Scholar 

  4. Conway, K. A., Harper, J. D., and Lansbury, P. T., Jr. (2000) Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry 39, 2552–2563.

    Article  PubMed  CAS  Google Scholar 

  5. Duyao, M. P., Auerbach, A. B., Ryan, A., Persichetti, F., Barnes, G. T., McNeil, S. M., et al. (1995) Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 269, 407–410.

    Article  PubMed  CAS  Google Scholar 

  6. Ohnishi, S., Koide, A., and Koide, S. (2000) Solution conformation and amyloid-like fibril formation of a polar peptide derived from a beta-hairpin in the OspA single-layer beta-sheet. J. Mol. Biol. 301, 477–489.

    Article  PubMed  CAS  Google Scholar 

  7. Turnell, W. G. and Finch, J. T. (1992) Binding of the dye congo red to the amyloid protein pig insulin reveals a novel homology amongst amyloid-forming peptide sequences. J. Mol. Biol. 227, 1205–1223.

    Article  PubMed  CAS  Google Scholar 

  8. Sipe, J. D. (1992) Amyloidosis. Annu. Rev. Biochem. 61, 947–975.

    Article  PubMed  CAS  Google Scholar 

  9. Booth, D. R., Sunde, M., Bellotti, V., Robinson, C. V., Hutchinson, W. L., Fraser, P. E., et al. (1997) Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 385, 787–793.

    Article  PubMed  CAS  Google Scholar 

  10. Hurle, M. R., Helms, L. R., Li, L., Chan, W., and Wetzel, R. (1994) A role for destabilizing amino acid replacements in light-chain amyloidosis. Proc. Natl. Acad. Sci. U. S. A. 91, 5446–5450.

    Article  PubMed  CAS  Google Scholar 

  11. Guijarro, J. I., Sunde, M., Jones, J. A., Campbell, I. D., and Dobson, C. M. (1998) Amyloid fibril formation by an SH3 domain. Proc. Natl. Acad. Sci. U. S. A. 95, 4224–4228.

    Article  PubMed  CAS  Google Scholar 

  12. Krebs, M. R., Wilkins, D. K., Chung, E. W., Pitkeathly, M. C., Chamberlain, A. K., Zurdo, J., et al. (2000) Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a peptide fragment from the beta-domain. J. Mol. Biol. 300, 541–549.

    Article  PubMed  CAS  Google Scholar 

  13. Schormann, N., Murrell, J. R., Liepnieks, J. J., and Benson, M. D. (1995) Tertiary structure of an amyloid immunoglobulin light chain protein: a proposed model for amyloid fibril formation. Proc. Natl. Acad. Sci. U.S.A. 92, 9490–9494.

    Article  PubMed  CAS  Google Scholar 

  14. Khurana, R., Gillespie, J. R., Talapatra, A., Minert, L. J., Ionescu-Zanetti, C., Millett, I., et al. (2001) Partially folded intermediates as critical precursors of light chain amyloid fibrils and amorphous aggregates. Biochemistry 40, 3525–3535.

    Article  PubMed  CAS  Google Scholar 

  15. Chiti, F., Taddei, N., Bucciantini, M., White, P., Ramponi, G., and Dobson, C. M. (2000) Mutational analysis of the propensity for amyloid formation by a globular protein. EMBO J. 19, 1441–1449.

    Article  PubMed  CAS  Google Scholar 

  16. Ramirez-Alvarado, M., Merkel, J. S., and Regan, L. (2000) A systematic exploration of the influence of the protein stability on amyloid fibril formation in vitro. Proc. Natl. Acad. Sci. U. S. A. 97, 8979–8984.

    Article  PubMed  CAS  Google Scholar 

  17. Shnyrov, V. L., Villar, E., Zhadan, G. G., Sanchez-Ruiz, J. M., Quintas, A., Saraiva, M. J., et al. (2000) Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin. Biophys. Chem. 88, 61–67.

    Article  PubMed  CAS  Google Scholar 

  18. McParland, V. J., Kalverda, A. P., Homans, S. W., and Radford, S. E. (2002) Structural properties of an amyloid precursor of beta(2)-microglobulin. Nat. Struct. Biol. 9, 326–331.

    Article  PubMed  CAS  Google Scholar 

  19. Martsev, S. P., Dubnovitsky, A. P., Vlasov, A. P., Hoshino, M., Hasegawa, K., Naiki, H., et al. (2002) Amyloid fibril formation of the mouse V(L) domain at acidic pH. Biochemistry 41, 3389–3395.

    Article  PubMed  CAS  Google Scholar 

  20. Kourie, J. I. and Henry, C. L. (2001) Protein aggregation and deposition: implications for ion channel formation and membrane damage. Croat. Med. J. 42, 359–374.

    PubMed  CAS  Google Scholar 

  21. Waschuk, S. A., Elton, E. A., Darabie, A. A., Fraser, P. E., and McLaurin, J. A. (2001) Cellular membrane composition defines A beta-lipid interactions. J. Biol. Chem. 276, 33561–33568.

    Article  PubMed  CAS  Google Scholar 

  22. Landau, L. D. and Lifshits, E. M. (1982) Theoretical physics. Electrodyn. Continuous Media 8, 60.

    Google Scholar 

  23. Uversky, V. N., Narizhneva, N. V., Kirschstein, S. O., Winter, S., and Lober, G. (1997) Conformational transitions provoked by organic solvents in beta-lactoglobulin: can a molten globule like intermediate be induced by the decrease in dielectric constant? Fold Des. 2, 163–172.

    Article  PubMed  CAS  Google Scholar 

  24. Ptitsyn, O. B. (1995) Structures of folding intermediates. Curr. Opin. Struct. Biol. 5, 74–78.

    Article  PubMed  CAS  Google Scholar 

  25. Buck, M. (1998) Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins. Q. Rev. Biophys. 31, 297–355.

    Article  PubMed  CAS  Google Scholar 

  26. Pertinhez, T. A., Bouchard, M., Smith, R. A., Dobson, C. M., and Smith, L. J. (2002) Stimulation and inhibition of fibril formation by a peptide in the presence of different concentrations of SDS. FEBS Lett. 529, 193–197.

    Article  PubMed  CAS  Google Scholar 

  27. Driscoll, P. C., Cyster, J. G., Campbell, I. D., and Williams, A. F. (1991) Structure of domain 1 of rat T lymphocyte CD2 antigen. Nature 353, 762–765.

    Article  PubMed  CAS  Google Scholar 

  28. Jones, E. Y., Davis, S. J., Williams, A. F., Harlos, K., and Stuart, D. I. (1992) Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2. Nature 360, 232–239.

    Article  PubMed  CAS  Google Scholar 

  29. Wyss, D. F., Choi, J. S., Li, J., Knoppers, M. H., Willis, K. J., Arulanandam, A. R., et al. (1995) Conformation and function of the N-linked glycan in the adhesion domain of human CD2. Science 269, 1273–1278.

    Article  PubMed  CAS  Google Scholar 

  30. Davis, S. J. and van der Merwe, P. A. (1996) The structure and ligand interactions of CD2: implications for T-cell function. Immunol. Today 17, 177–187.

    Article  PubMed  CAS  Google Scholar 

  31. Yang, J. J., Carroll, A. R., Yang, W., Ye, Y., and Nguyen, C. N. (2000) Nonnative intermediate state of acid-stable betasheet protein. Cell Biochem. Biophys. 33, 253–273.

    Article  PubMed  CAS  Google Scholar 

  32. Yang, J. J., Ye, Y., Carroll, A., Yang, W., and Lee, H. W. (2001) Structural biology of the cell adhesion protein CD2: alternatively folded states and structure-function relation. Curr. Protein. Pept. Sci. 2, 1–17.

    Article  PubMed  CAS  Google Scholar 

  33. Yang, J. J., Yang, H., Ye, Y., Hopkins, H., Jr., and Hastings, G. (2002) Temperature-induced formation of a non-native intermediate state of the all beta-sheet protein CD2. Cell Biochem. Biophys. 36, 1–18.

    PubMed  CAS  Google Scholar 

  34. Semisotnov, G. V., Rodionova N. A., Razgulyaev, O. I., Uversky, V. N., Gripas, A. F., and Gilmanshin, R. I. (1991) Study of the “molten globule” intermediate state in protein folding by a hydrophobic fluorescent probe. Biopolymers 31, 119–128.

    Article  PubMed  CAS  Google Scholar 

  35. Yang, J. J., van den Berg, B., Pitkeathly, M., Smith, L. J., Bolin, K.A., Keiderling, T. A., et al. (1996) Native-like secondary structure in a peptide from the alpha-domain of hen lysozyme. Fold Des. 1, 473–484.

    Article  PubMed  CAS  Google Scholar 

  36. Yang, J. J., Buck, M., Pitkeathly, M., Kotik, M., Haynie, D. T., Dobson, C. M., et al. (1995) Conformational properties of four peptides spanning the sequence of hen lysozyme. J. Mol. Biol. 252, 483–491.

    Article  PubMed  CAS  Google Scholar 

  37. McParland, V. J., Kad, N. M., Kalverda, A. P., Brown, A., Kirwin-Jones, P., Hunter, M. G., et al. (2000) Partially unfolded states of beta(2)-microglobulin and amyloid formation in vitro. Biochemistry 39, 8735–8746.

    Article  PubMed  CAS  Google Scholar 

  38. Ladewig, P. (1945) Double-refringence of the amyloid-congo red-complex in histological sections. Nature 156, 81–82.

    Google Scholar 

  39. Gross, M., Wilkins, D. K., Pitkeathly, M. C., Chung, E. W., Higham, C., Clark, A., et al. (1999) Formation of amyloid fibrils by peptides derived from the bacterial cold shock protein CspB. Protein Sci. 8, 1350–1357.

    Article  PubMed  CAS  Google Scholar 

  40. Klunk, W. E., Jacob, R. F., and Mason, R. P. (1999) Quantifying amyloid by congo red spectral shift assay. Meth. Enzymol. 309, 285–305.

    PubMed  CAS  Google Scholar 

  41. Wilkins, D. K., Dobson, C. M., and Gross, M. (2000) Biophysical studies of the development of amyloid fibrils from a peptide fragment of cold shock protein B. Eur. J. Biochem. 267, 2609–2616.

    Article  PubMed  CAS  Google Scholar 

  42. Chiti, F., Webster, P., Taddei, N., Clark, A., Stefani, M., Ramponi, G., et al. (1999) Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc. Natl. Acad. Sci. U. S. A. 96, 3590–3594.

    Article  PubMed  CAS  Google Scholar 

  43. Rochet, J. C. and Lansbury, P. T., Jr. (2000) Amyloid fibrillogenesis: themes and variations. Curr. Opin. Struct. Biol. 10, 60–68.

    Article  PubMed  CAS  Google Scholar 

  44. LeVine, H., 3rd (1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Meth. Enzymol. 309, 274–284.

    Article  PubMed  CAS  Google Scholar 

  45. Chiti, F., Taddei, N., Webster, P., Hamada, D., Fiaschi, T., Ramponi, G., et al. (1999) Acceleration of the folding of acylphosphatase by stabilization of local secondary structure. Nat. Struct. Biol. 6, 380–387.

    Article  PubMed  CAS  Google Scholar 

  46. Olofsson, S., and Baltzer, L. (1996) Structure and dynamics of a designed helix-loop-helix dimer in dilute aqueous trifluoroethanol solution. A strategy for NMR spectroscopic structure determination of molten globules in the rational design of native-like proteins. Fold Des. 1, 347–356.

    Article  PubMed  CAS  Google Scholar 

  47. Konno, T. (1998) Conformational diversity of acid-denatured cytochrome c studied by a matrix analysis of far-UV CD spectra. Protein Sci. 7, 975–982.

    Article  PubMed  CAS  Google Scholar 

  48. Zerovnik, E., Jerala, R., Virden, R., Kroon Zitko, L., Turk, V., and Waltho, J. P. (1998) On the mechanism of human stefin B folding: II. Folding from GuHCl unfolded, TFE denatured, acid denatured, and acid intermediate states. Proteins 32, 304–313.

    Article  PubMed  CAS  Google Scholar 

  49. Fandrich, M., Fletcher, M. A., and Dobson, C. M. (2001) Amyloid fibrils from muscle myoglobin. Nature 410, 165–166.

    Article  PubMed  CAS  Google Scholar 

  50. Pertinhez, T. A., Bouchard, M., Tomlinson, E. J., Wain, R., Ferguson, S. J., Dobson, C. M., et al. (2001) Amyloid fibril formation by a helical cytochrome. FEBS Lett. 495, 184–186.

    Article  PubMed  CAS  Google Scholar 

  51. Souillac, P. O., Uversky, V. N., Millett, I. S., Khurana, R., Doniach, S., and Fink, A. L. (2002) Effect of association state and conformational stability on the kinetics of immunoglobulin light chain amyloid fibril formation at physiological pH. J. Biol. Chem. 277, 12657–12665.

    Article  PubMed  CAS  Google Scholar 

  52. Souillac, P. O., Uversky, V. N., Millett, I. S., Khurana, R., Doniach, S., and Fink, A. L. (2002) Elucidation of the molecular mechanism during the early events in immunoglobulin light chain amyloid fibrillation. Evidence for an off-pathway oligomer at acidic pH. J. Biol. Chem. 277, 12666–12679.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, Center of Drug Design, Georgia State University, Atlanta, GA

    Amy Carroll, Wei Yang, Yiming Ye & Jenny J. Yang

  2. Department of Biology, Center of Drug Design, Georgia State University, Atlanta, GA

    Robert Simmons

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  1. Amy Carroll
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  2. Wei Yang
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Correspondence to Jenny J. Yang.

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Carroll, A., Yang, W., Ye, Y. et al. Amyloid fibril formation by a domain of rat cell adhesion molecule. Cell Biochem Biophys 44, 241–249 (2006). https://doi.org/10.1385/CBB:44:2:241

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