The non-core regions of human lysozyme amyloid fibrils influence cytotoxicity.

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 :

Pages :

783-96

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954362/pdf/main.pdf

Commentary :

Available on ORBi :

since 04 November 2010

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