Common molecular pathogenesis of disease-related intrinsically disordered proteins revealed by NMR analysis.
 

Common molecular pathogenesis of disease-related intrinsically disordered proteins revealed by NMR analysis.

Common molecular pathogenesis of disease-related intrinsically disordered proteins revealed by NMR analysis.

J Biochem. 2017 Sep 11;:

Authors: Shigemitsu Y, Hiroaki H

Abstract
Intrinsically disordered proteins (IDPs) are either completely unstructured or contain large disordered regions in their native state; they have drawn much attention in the field of molecular pathology. Some of them substantially tend to form protein self-assemblies, such as toxic or non-toxic aggregates and fibrils, and have been postulated to relate to diseases. These disease-related IDPs include A?(1-42) [Alzheimer's disease (AD)], Tau (AD and tauopathy), ?-synuclein (Parkinson's disease), and p53 (cancer). Several studies suggest that these aggregation and/or fibril formation processes are often initiated by transient conformational changes of the IDPs prior to protein self-assembly. Interestingly, the pathological molecular processes of these IDPs share multiple common features with those of protein misfolding diseases, such as transmissible spongiform encephalopathy (PrPsc) and AL-amyloidosis (VL-domain of ?-immunoglobulin). This review provides an overview of solution NMR techniques that can help analyze the early and transient events of conformational equilibrium of IDPs and folded proteins.


PMID: 28992347 [PubMed - as supplied by publisher]



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