Uversky

Vladimir N. Uversky

Department of Molecular Medicine

University of South Florida

 

12:20 p.m. Friday, April 14, 2017

Biocomplexity Institute Conference Center (room 145)

 

 

 

 

Abstract

 

Intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structure under physiological conditions in vitro. They are highly abundant in nature and have functional repertoire which is very broad and complements functions of ordered proteins. Often, intrinsically disordered proteins are involved in regulation, signaling and control pathways. Functions of IDPs may arise from the specific disordered form, from inter-conversion of disordered forms, or from transitions between disordered and ordered as well as between ordered and disordered conformations. The choice between these conformations is determined by the peculiarities of the protein environment, and many IDPs possess an exceptional ability to fold in a template-dependent manner. These proteins are often key players in protein-protein interaction networks being highly abundant among hubs. Regions of mRNA which undergo alternative splicing code for disordered proteins more often than they code for structured proteins. This association of alternative splicing and intrinsic disorder helps proteins to avoid folding difficulties and provides a novel mechanism for developing tissue-specific protein interaction networks. IDPs are tightly controlled in the norm by various genetic and non-genetic mechanisms. Alteration in regulation of this disordered regulators are often detrimental to a cell and many IDPs are associated with a variety of human diseases such as cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, diabetes and others. Therefore, there is an intriguing interconnection between intrinsic disorder, cell signaling and human diseases. Pathogenic IDPs, such as α-synuclein, tau protein, p53, BRCA1 and many other disease-associated hub proteins represent attractive targets for drugs modulating protein-protein interactions. Several strategies have been elaborated for elucidating the mechanisms of blocking of the intrinsic disorder-based protein-protein interactions.

 

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