title: From Disorder to Mis-Order: Structural Aspects of Pathogenic Oligomerization in Conformational Diseases.
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.
authors.affiliation: 11/F, Block 1, La Costa, Po Tai Street, Ma On Shan. Hong Kong.
authors.forename: Chin Pang Benny
authors.initials: CPB
authors.lastname: Yiu
authors.affiliation: Department of Applied Biology and Chemical Technology and The State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hunghom, Kowloon. Hong Kong.
authors.forename: Yu Wai
authors.initials: YW
authors.lastname: Chen
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D055808:Drug Discovery; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000682:Amyloid; D064267:Intrinsically Disordered Proteins
keywords: IDP; Misfolding; aggregation; intrinsically disordered proteins; neurodegeneration; oligomerization