Abstract
Proteins implicated in neurological conformational diseases contain substantial amounts of “intrinsic disorder”. These native monomeric functional states may transit into some oligomeric states that have high β-sheet contents and seed the formation of insoluble amyloid fibrils. The prevailing view is that these “toxic” oligomers should be targeted for drug development. Here, an overview of the diseases was presented, within the general framework of the oligomerization of intrinsically disordered proteins. These systems pose some specific challenges to structural studies: the toxic oligomers are transient, low in concentration, and often need to be studied in a heterogeneous environment. Nevertheless, there have been much exciting progress as a result of the creative use of experimental techniques, a selection of these were outlined.
Keywords: Misfolding, neurodegeneration, intrinsically disordered proteins, IDP, oligomerization, aggregation.
Protein & Peptide Letters
Title:From Disorder to Mis-Order: Structural Aspects of Pathogenic Oligomerization in Conformational Diseases
Volume: 24 Issue: 4
Author(s): Chin Pang Benny Yiu and Yu Wai Chen
Affiliation:
Keywords: Misfolding, neurodegeneration, intrinsically disordered proteins, IDP, oligomerization, aggregation.
Abstract: Proteins implicated in neurological conformational diseases contain substantial amounts of “intrinsic disorder”. These native monomeric functional states may transit into some oligomeric states that have high β-sheet contents and seed the formation of insoluble amyloid fibrils. The prevailing view is that these “toxic” oligomers should be targeted for drug development. Here, an overview of the diseases was presented, within the general framework of the oligomerization of intrinsically disordered proteins. These systems pose some specific challenges to structural studies: the toxic oligomers are transient, low in concentration, and often need to be studied in a heterogeneous environment. Nevertheless, there have been much exciting progress as a result of the creative use of experimental techniques, a selection of these were outlined.
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Cite this article as:
Yiu Pang Benny Chin and Chen Wai Yu, From Disorder to Mis-Order: Structural Aspects of Pathogenic Oligomerization in Conformational Diseases, Protein & Peptide Letters 2017; 24 (4) . https://dx.doi.org/10.2174/0929866524666170220111930
DOI https://dx.doi.org/10.2174/0929866524666170220111930 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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