Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly.

ABSTRACT: Self-assembly of misfolded proteins into ordered fibrillar aggregates known as amyloid results in numerous human diseases. Despite an increasing number of proteins and peptide fragments being recognised as amyloidogenic, how these amyloid aggregates assemble remains unclear. In particular, the identity of the nucleating species, an ephemeral entity that defines the rate of fibril formation, remains a key outstanding question. Here, we propose a new strategy for analyzing the self-assembly of amyloid fibrils involving global analysis of a large number of reaction progress curves and the subsequent systematic testing and ranking of a large number of possible assembly mechanisms. Using this approach, we have characterized the mechanism of the nucleation-dependent formation of beta(2)-microglo

SUBMITTER: Xue WF 

PROVIDER: S-EPMC2440360 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature