Glimpses of the Molecular Mechanisms of Beta2-microglobulin Fibril Formation in Vitro: Aggregation on a Complex Energy Landscape

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2009 May 13

PMID 19433089

Citations 30

Authors

Geoffrey W Platt

Sheena E Radford

Affiliations

Soon will be listed here.

Abstract

Beta(2)-microglobulin (beta(2)m) is a 99-residue protein that aggregates to form amyloid fibrils in dialysis-related amyloidosis. The protein provides a powerful model for exploration of the structural molecular mechanisms of fibril formation from a full-length protein in vitro. Fibrils have been assembled from beta(2)m under both low pH conditions, where the precursor is disordered, and at neutral pH where the protein is initially natively folded. Here we discuss the roles of sequence and structure in amyloid formation, the current understanding of the structural mechanisms of the early stages of aggregation of beta(2)m at both low and neutral pH, and the common and distinct features of these assembly pathways.

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