Vladimir N. Uversky | University of South Florida

Ph.D Nanoscale Science Seminar Series | Spring 2016

Vladimir N. Uversky
University of South Florida

Department of Molecular Medicine

“Intrinsically disordered proteins in the norm and pathology”


Intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structure under physiological conditions in vitro, often resembling 'protein clouds'. Amino acid sequences of IDPs are characterized by several easily recognizable features. In addition to their peculiar sequence characteristics IDPs have several unusual biophysical features, such as sequential, structural, and spatiotemporal heterogeneity; rough and relatively flat energy landscapes; ability to undergo both induced folding and induced unfolding; the ability to interact specifically with structurally unrelated partners; the ability to gain different structures at binding to different partners; and the ability to keep essential amount of disorder even in the bound form. Some IDPs are also characterized by the “turned-out” response to the changes in their environment. It is proposed that the heterogeneous spatiotemporal structure of IDPs can be described as a set of foldons, inducible foldons, semi-foldons and non-foldons. They may lose their function when folded, and activation of some IDPs is associated with the awaking of the dormant disorder. They are highly abundant in nature and have a very broad functional repertoire which 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 a-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.


Dr. Vladimir N. Uversky received his B.S. and M.S. degrees in Physics from Leningrad State University in Russia in 1986. He then completed his Ph.D. degree in Physics and Mathematics (field of study -Biophysics) at the Moscow Institute of Technical Physics in 1991 and the Doctor of Sciences (D.Sc.) degree in Physics and Mathematics (field of study - Biophysics) at the Institute Experimental and Theoretical Biophysics of the Russian Academy of Sciences in 1998. He is currently an Associate Professor at the Department of Molecular Medicine in the University of South Florida, College of Medicine. Dr. Uversky is the author or co-author of more than 550 peer-reviewed publications (cited more than 28,000 times), 65 book chapters, the editor of 20 scientific books and 5 book series, and more than 15 journals. His major research interests are related to protein structure, folding, misfolding and non-folding.

Thursday, April 7, 2016 @ 3:30 PM in Burson 115
Refreshments served at 3:15 PM

Burson 115
Thursday, April 7, 2016 - 15:30
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