The non-core regions of human lysozyme amyloid fibrils influence cytotoxicity.
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-β 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.
Mossuto
Maria F
MF
Institute for Research in Biomedicine, Barcelona, Spain.
Dhulesia
Anne
A
Devlin
Glyn
G
Frare
Erica
E
Kumita
Janet R
JR
de Laureto
Patrizia Polverino
PP
Dumoulin
Mireille
M
Fontana
Angelo
A
Dobson
Christopher M
CM
Salvatella
Xavier
X
D000682:Amyloid / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000737:chemistry / Q000633:toxicity*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D055550:Protein Stability; D013055:Spectrophotometry, Infrared; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D000682:Amyloid; D013778:Tetrazolium Salts; D013844:Thiazoles; D009113:Muramidase; C022616:thiazolyl blue