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Article
Nature 385, 787 - 793 (27 February 1997); doi:10.1038/385787a0

Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis

David R. Booth*, Margaret Sunde, Vittorio Bellotti*, Carol V. Robinson, Winston L. Hutchinson*, Paul E. Fraser§, Philip N. Hawkins*, Christopher M. Dobson, Sheena E. Radford, Colin C. F. Blake & Mark B. Pepys*

*Immunological Medicine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
Laboratory of Molecular Biophysics and New Chemistry Laboratory, Oxford Centre for Molecular Sciences, University of Oxford, Oxford OX1 3QT, UK
§Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto M5S 3H2, Canada
These authors contributed equally to this work.
Present addresses: Dipartimento di Biochimica, Università di Pavia, Via Taramelli 3B, 27100 Pavia, Italy (V.B.); Department of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK (S.E.R.).

Tissue deposition of soluble proteins as amyloid fibrils underlies a range of fatal diseases. The two naturally occurring human lysozyme variants are both amyloidogenic, and are shown here to be unstable. They aggregate to form amyloid fibrils with transformation of the mainly helical native fold, observed in crystal structures, to the amyloid fibril cross-β fold. Biophysical studies suggest that partly folded intermediates are involved in fibrillogenesis, and this may be relevant to amyloidosis generally.

  1. Pepys, M. B. in Samter's Immunologic Diseases (eds Frank, M. M., Austen, K. F., Claman, H. N. & Unanue, E. R.) 637−655 (Little, Brown and Company, Boston, 1994).
  2. Tan, S. Y. & Pepys, M. B. Amyloidosis. Histopathology 25, 403−414 (1994). | PubMed | ISI | ChemPort |
  3. Glenner, G. G. Amyloid deposits and amyloidosis—the beta-fibrilloses. I. N. Engl. J. Med. 302, 1283−1292 (1980). | PubMed | ISI | ChemPort |
  4. Blake, C. C. F. & Serpell, L. C. Synchrotron X-ray studies suggest that the core of the transthyretin amyloid fibril is a continuous beta-sheet helix. Structure 4, 989−998 (1996). | Article | PubMed | ISI | ChemPort |
  5. Fraser, P. E. et al. Fibril formation by primate, rodent and Dutch-hemorrhagic analogues of Alzheimer beta-protein. Biochemistry 31, 10716−10723 (1992). | Article | PubMed | ISI | ChemPort |
  6. Goldfarb, L. G., Brown, P., Haltia, M., Ghiso, J. & Frangione, B. Synthetic peptides corresponding to different mutated regions of the amyloid gene in familial Creutzfeldt-Jakob disease show enhanced in vitro formation of morphologically different amyloid fibrils. Proc. Natl Acad. Sci. USA 90, 4451−4454 (1993). | PubMed | ChemPort |
  7. Abrahamson, M. & Grubb, A. Increased body temperature accelerates aggregation of the Leu-68-Gln mutant cystatin C, the amyloid-forming protein in hereditary cystatin C amyloid angiopathy. Proc. Natl Acad. Sci. USA 91, 1416−1420 (1994). | PubMed | ChemPort |
  8. Hurle, M. R., Helms, L. R., Li, L., Chan, W. & Wetzel, R. A role for destabilizing amino acid replacements in light-chain amyloidosis. Proc. Natl Acad. Sci. USA 91, 5446−5450 (1994). | PubMed | ChemPort |
  9. Maury, C. P. J., Nurmiaho-Lassila, E.-L. & Rossi, H. Amyloid fibril formation in gelsolin-derived amyloidosis. Definition of the amyloidogenic region and evidence of accelerated amyloid formation of mutant Asn-187 and Tyr-187 gelsolin peptides. Lab. Invest. 70, 558−564 (1994). | PubMed | ISI | ChemPort |
  10. Yamada, T., Kluve-Beckerman, B., Liepnicks, J. J. & Benson, M. D. Fibril formation from recombinant human serum amyloid A. Biochim. Biophys. Acta 1226, 323−329 (1994). | Article | PubMed | ISI | ChemPort |
  11. McCutchen, S. L., Lai, Z., Miroy, G. J., Kelly, J. W. & Colon, W. Comparison of lethal and nonlethal transthyretin variants and their relationship to amyloid disease. Biochemistry 34, 13527−13536 (1995). | Article | PubMed | ISI | ChemPort |
  12. Lansbury, P. T. Jr et al. Structural model for the beta-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide. Nature Struct. Biol. 2, 990−998 (1995). | Article | PubMed | ISI | ChemPort |
  13. Kelly, J. W. Alternative conformations of amyloidogenic proteins govern their behaviour. Curr. Opin. Struct. Biol. 6, 11−17 (1996). | Article | PubMed | ISI | ChemPort |
  14. Booth, D. R. et al. Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene. J. Clin. Invest. 98, 2714−2721 (1996). | PubMed | ISI | ChemPort |
  15. Pepys, M. B. et al. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature 362, 553−557 (1993). | Article | PubMed | ISI | ChemPort |
  16. Blake, C. C. F. et al. Structure of hen egg-white lysozyme. Nature 206, 757−761 (1965). | PubMed | ISI | ChemPort |
  17. Blake, C. C., Pulford, W. C. & Artymiuk, P. J. X-ray studies of water in crystals oflysozyme. J. Mol. Biol. 167, 693−723 (1983). | PubMed | ChemPort |
  18. Artymiuk, P. J. & Blake, C. C. F. Refinement of human lysozyme at 1.5 Å resolution analysis of non-bonded and hydrogen-bond interactions. J. Mol. Biol. 152, 737−762 (1981). | Article | PubMed | ChemPort |
  19. McKenzie, H. A. & White, F. H. Jr Lysozyme and alpha-lactalbumin: structure, function, and interrelationship. Adv. Protein Chem. 41, 173−315 (1991). | PubMed | ChemPort |
  20. Radford, S. E., Dobson, C. M. & Evans, P. A. The folding of hen lysozyme involves partially structured intermediates and multiple pathways. Nature 358, 302−307 (1992). | Article | PubMed | ISI | ChemPort |
  21. Radford, S. E. & Dobson, C. M. Insights into protein folding using physical techniques: studies of lysozyme and alpha-lactalbumin. Phil. Trans. R. Soc. Lond. B 348, 17−25 (1995). | ISI | ChemPort |
  22. Kuwajima, K. The molten globule state as a clue for understanding the folding and cooperativity of globular-protein structure. Proteins Struct. Funct. Genet. 6, 87−103 (1989). | PubMed | ISI | ChemPort |
  23. Ptitsyn, O. B. Molten globule and protein folding. Adv. Protein Chem. 47, 83−229 (1995). | PubMed | ISI | ChemPort |
  24. Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F. & Whitehouse, C. M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64−71 (1989). | PubMed | ISI | ChemPort |
  25. Shih, P., Holland, D. R. & Kirsch, J. F. Thermal stability determinants of chicken egg-white lysozyme core mutants: hydrophobicity, packing volume, and conserved buried water molecules. Protein Sci. 4, 2050−2062 (1995). | PubMed | ISI | ChemPort |
  26. Puchtler, H., Sweat, F. & Levine, M. On the binding of Congo red by amyloid. J. Histochem. Cytochem. 10, 355−364 (1995).
  27. Harrison, R. F. et al. 'Fragile' liver and massive hepatic haemorrhage due to hereditary amyloidosis. Gut 38, 151−152 (1996). | PubMed | ChemPort |
  28. Stott, K., Blackburn, J. M., Butler, P. J. & Perutz, M. Incorporation of glutamine repeats makes protein oligomerize: implications for neurodegenerative diseases. Proc. Natl Acad. Sci. USA 92, 6509−6513 (1995). | PubMed | ChemPort |
  29. Nelson, S. R., Lyon, M., Gallagher, J. T., Johnson, E. A. & Pepys, M. B. Isolation and characterization of the integral glycosaminoglycan constituents of human amyloid A and monoclonal light-chain amyloid fibrils. Biochem. J. 275, 67−73 (1991). | PubMed | ChemPort |
  30. Haezebrouck, P. et al. An equilibrium partially folded state of human lysozyme at low pH. J. Mol. Biol. 246, 382−387 (1995). | Article | PubMed | ISI | ChemPort |
  31. Wu, L. C., Peng, Z.-y. & Kim, P. S. Bipartite structure of the alpha-lactalbumin molten globule. Nature Struct. Biol. 2, 281−286 (1995). | Article | PubMed | ISI | ChemPort |
  32. Eyles, S. J., Radford, S. E., Robinson, C. V. & Dobson, C. M. Kinetic consequences of the removal of a disulfide bridge on the folding of hen lysozyme. Biochemistry 33, 13038−13048 (1994). | Article | PubMed | ISI | ChemPort |
  33. Robinson, C. V. et al. Conformation of GroEL-bound alpha-lactalbumin probed by mass spectrometry. Nature 372, 646−651 (1994). | Article | PubMed | ISI | ChemPort |
  34. Yang, J. J., Pitkeathly, M. & Radford, S. E. Far-UV circular dichroism reveals a conformational switch in a peptide fragment from the beta-sheet of hen lysozyme. Biochemistry 33, 7345−7353 (1994). | Article | PubMed | ChemPort |
  35. Minor, D. L. Jr & Kim, P. S. Context-dependent secondary structure formation of a designed protein sequence. Nature 380, 730−734 (1996). | Article | PubMed | ISI | ChemPort |
  36. Dobson, C. M. Finding the right fold. Nature Struct. Biol. 2, 513−517 (1995). | Article | PubMed | ISI | ChemPort |
  37. Bychkova, V. E. & Ptitsyn, O. B. Folding intermediates are involved in genetic diseases? FEBS Lett. 359, 6−8 (1995). | Article | PubMed | ChemPort |
  38. Riek, R. et al. NMR structure of the mouse prion protein domain PrP (121−321). Nature 382, 180−182 (1996). | Article | PubMed | ISI | ChemPort |
  39. Chung, L. P., Keshav, S. & Gordon, S. Cloning the human lysozyme cDNA: inverted Alu repeat in the mRNA and in situ hybridization for macrophages and Paneth cells. Proc. Natl Acad. Sci. USA 85, 6227−6231 (1988). | PubMed | ChemPort |
  40. Osserman, E. F. & Lawlor, D. P. Serum and urinary lysozymes (muramidase) in monocytic and monomyelocytic leukemia. J. Exp. Med. 124, 921−951 (1996).
  41. Nanjo, F., Sakai, K. & Usui, T. p-nitrophenol pent-N-acetyl-beta-chitopentaoside as a novel synthetic substrate for the colorimetric assay of lysozyme. J. Biochem. 104, 255−258 (1988). | PubMed | ChemPort |
  42. Otwinowski, Z. in Proceedings of the CCP4 Study Weekend (eds Sawyer, L., Isaacs, N. & Bailey, S.) (SERC Daresbury Laboratory, Warrington, UK, 1993).
  43. CCP4 The CCP4 Suite: programs for protein crystallography. Acta Crystallogr. D 50, 760−763 (1994). | Article | ISI |
  44. Brünger, A. T. X-PLOR manual version 3.0 (Yale University, New Haven, CT, 1992).
  45. Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, M. Improved methods for the building of protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 74, 110−119 (1991).
  46. Kraulis, P. J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946−950 (1991). | Article | ISI |
  47. Perry, L. J. & Wetzel, R. Unpaired cysteine-54 interferes with the ability of an engineered disulfide to stabilize T4 lysozyme. Biochemistry 25, 733−739 (1986). | Article | PubMed | ChemPort |
  48. Bai, Y., Milne, J. S., Mayne, L. & Englander, S. W. Primary structure effects on peptide group hydrogen exchange. Proteins Struct. Funct. Genet. 17, 75−86 (1993). | PubMed | ISI | ChemPort |
  49. Funahashi, J., Takano, K., Ogasahara, K., Yamagata, Y. & Yutani, K. The structure, stability, and folding process of amyloidogenic mutant human lysozyme. J. Biochem. 120, 1216−1223 (1996). | PubMed | ISI | ChemPort |



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