Article (Scientific journals)
The non-core regions of human lysozyme amyloid fibrils influence cytotoxicity.
Mossuto, Maria F; Dhulesia, Anne; Devlin, Glyn et al.
2010In Journal of Molecular Biology, 402 (5), p. 783-96
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Keywords :
Amyloid/chemistry/toxicity; Cell Line; Cell Survival; Humans; Microscopy, Electron, Transmission; Muramidase/chemistry/toxicity; Neurons/metabolism/physiology; Protein Stability; Spectrophotometry, Infrared; Tetrazolium Salts/metabolism; Thiazoles/metabolism
Abstract :
[en] Identifying the cause of the cytotoxicity of species populated during amyloid formation is crucial to understand the molecular basis of protein deposition diseases. We have examined different types of aggregates formed by lysozyme, a protein found as fibrillar deposits in patients with familial systemic amyloidosis, by infrared spectroscopy, transmission electron microscopy, and depolymerization experiments, and analyzed how they affect cell viability. We have characterized two types of human lysozyme amyloid structures formed in vitro that differ in morphology, molecular structure, stability, and size of the cross-beta core. Of particular interest is that the fibrils with a smaller core generate a significant cytotoxic effect. These findings indicate that protein aggregation can give rise to species with different degree of cytotoxicity due to intrinsic differences in their physicochemical properties.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Mossuto, Maria F
Dhulesia, Anne
Devlin, Glyn
Frare, Erica
Kumita, Janet R
Polverino de Laureto, Patrizia
Dumoulin, Mireille  ;  Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Fontana, Angelo
Dobson, Christopher M
Salvatella, Xavier
Language :
English
Title :
The non-core regions of human lysozyme amyloid fibrils influence cytotoxicity.
Publication date :
2010
Journal title :
Journal of Molecular Biology
ISSN :
0022-2836
eISSN :
1089-8638
Publisher :
Academic Press, London, United Kingdom
Volume :
402
Issue :
5
Pages :
783-96
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Available on ORBi :
since 04 November 2010

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