Lysozyme: a paradigmatic molecule for the investigation of protein structure, function and misfolding.
BACKGROUND
The term amyloidosis encompasses a wide group of conditions characterised by the tissue deposition of autologous proteins assembled in homogeneous regularly spaced antiparallel beta strands. The mechanism by which the different proteins gain a conformation, allowing monomers to bind to each other to form the regular amyloid fibril, is under intensive investigation. The discovery that human lysozyme, a protein thoroughly structurally and functionally characterised, can form amyloid fibrils has offered unique opportunities to unveil the molecular mechanisms involved in amyloid formation. Four amyloidogenic mutations have been identified and an apparently non-amyloidogenic polymorphism has been recently described.


CONCLUSIONS
Lysozyme is well characterised for structure, function, folding dynamics and metabolism and comparative studies are becoming available that highlight pathogenic differences between the wild-type and the amyloidogenic variants. The chemical structure of lysozyme in natural amyloid fibrils was characterised in high detail in the early cases, but it is still lacking in the cases most recently discovered. Amyloidogenic lysozymes represent a prototypic molecule for new pharmaceutical approaches in which the formation of amyloid fibrils is abrogated through a stabilisation of the precursor.
Merlini
Giampaolo
G
Biotechnology Research Laboratory, University Hospital IRCCS Policlinico San Matteo, Department of Biochemistry, University of Pavia, P.le Golgi, 2, 27100 Pavia, Italy. gmerlini@unipv.it
Bellotti
Vittorio
V
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008024:Ligands; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding
D000682:Amyloid; D008024:Ligands; D009113:Muramidase