Fiber-dependent amyloid formation as catalysis of an existing reaction pathway.

ABSTRACT: A central component of a number of degenerative diseases is the deposition of protein as amyloid fibers. Self-assembly of amyloid occurs by a nucleation-dependent mechanism that gives rise to a characteristic sigmoidal reaction profile. The abruptness of this transition is a variable characteristic of different proteins with implications to both chemical mechanism and the aggressiveness of disease. Because nucleation is defined as the rate-limiting step, we have sought to determine the nature of this step for a model system derived from islet amyloid polypeptide. We show that nucleation occurs by two pathways: a fiber-independent (primary) pathway and a fiber-dependent (secondary) pathway. We first show that the balance between primary and secondary contributions can be manipulated by an e

SUBMITTER: Ruschak AM 

PROVIDER: S-EPMC1941471 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature