Effect of DTT on Fibrillogenesis of Lysozyme
Date Issued
2007
Date
2007
Author(s)
Wang, Bo-Wei
DOI
zh-TW
Abstract
At least twenty different human proteins can fold abnormally to form fibrillar protein deposits which lead to so-called amyloid disease or amyloidoses. During the progression of these disease, these amyloidogenic proteins can self-assemble into stable fibrils with extensive ß-sheet conformation. While it is widely recognized that the dysfunction and concomitant death of cells is caused by the nearby protein aggregates, the underlying mechanism of amyloid diseases remains far from clear.
The research presented here is aimed at exploring the effect of DTT on the in vitro fibril formation of hen egg-white lysozymes with four disulfide bonds. In this work, we specifically addressed (a) the effect of DTT concentration under different incubation temperatures on the hen lysozyme structure and fibril formation, (b) the effect of addition of DTT at later time points on the amyloid fibrillization of hen lysozymes, and (c) the effect of concentration ratio between reduced and oxidized forms of DTT on the fibril formation of lysozymes. We first demonstrated that the rate of fibril formation of hen lysozyme increased with incubation temperature; however, the content of amyloid fibrils was not the function of incubation temperature. Next, we showed that the inhibition of lysozyme amyloid formation by DTT owing to the breakage of disulfide bonds. Also, no inhibitory effect was observed if DTT was added at 12 hours after the launch of aggregation on hen lysozyme fibrillogenesis. Finally, we found that the oxidized form of DTT did not exhibit any inhibitory potency against amyloid fibril formation. The current research not only investigates the mechanism of amyloid protein self-assembly, but also examines the structures of lysozyme species during the course of aggregation process. We believe the outcome from this work will certainly further our understanding of the molecular mechanism(s) of amyloid diseases.
Subjects
溶菌酶
二硫代蘇糖醇
類澱粉纖維
雙硫鍵
聚集體
lysozyme
DTT
amyloid fibril
disulfide bonds
aggregate
SDGs
Type
thesis
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