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Understanding the complex mechanisms of ?2-microglobulin amyloid assembly.

ABSTRACT: Several protein misfolding diseases are associated with the conversion of native proteins into ordered protein aggregates known as amyloid. Studies of amyloid assemblies have indicated that non-native proteins are responsible for initiating aggregation in vitro and in vivo. Despite the importance of these species for understanding amyloid disease, the structural and dynamic features of amyloidogenic intermediates and the molecular details of how they aggregate remain elusive. This review focuses on recent advances in developing a molecular description of the folding and aggregation mechanisms of the human amyloidogenic protein ?(2)-microglobulin under physiologically relevant conditions. In particular, the structural and dynamic properties of the non-native folding intermediate I(T) and its role in the initiation of fibrillation and the development of dialysis-related amyloidosis are discussed.

SUBMITTER: Eichner T

PROVIDER: S-EPMC3229708 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Understanding the complex mechanisms of β2-microglobulin amyloid assembly.

Eichner Timo T Radford Sheena E SE

The FEBS journal 20110613 20

Several protein misfolding diseases are associated with the conversion of native proteins into ordered protein aggregates known as amyloid. Studies of amyloid assemblies have indicated that non-native proteins are responsible for initiating aggregation in vitro and in vivo. Despite the importance of these species for understanding amyloid disease, the structural and dynamic features of amyloidogenic intermediates and the molecular details of how they aggregate remain elusive. This review focuses ...[more]

PMID: 21595827

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