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2019

University of South Florida

Molecular Medicine Faculty Publications

Intrinsically Disordered Protein

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Intrinsic Disorder-Based Emergence In Cellular Biology: Physiological And Pathological Liquid-Liquid Phase Transitions In Cells, April L. Darling, Boris Zaslavsky, Vladimir N. Uversky Jan 2019

Intrinsic Disorder-Based Emergence In Cellular Biology: Physiological And Pathological Liquid-Liquid Phase Transitions In Cells, April L. Darling, Boris Zaslavsky, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The visible outcome of liquid-liquid phase transitions (LLPTs) in cells is the formation and disintegration of various proteinaceous membrane-less organelles (PMLOs). Although LLPTs and related PMLOs have been observed in living cells for over 200 years, the physiological functions of these transitions (also known as liquid-liquid phase separation, LLPS) are just starting to be understood. While unveiling the functionality of these transitions is important, they have come into light more recently due to the association of abnormal LLPTs with various pathological conditions. In fact, several maladies, such as various cancers, different neurodegenerative diseases, and cardiovascular diseases, are known to be …


Supramolecular Fuzziness Of Intracellular Liquid Droplets: Liquid–Liquid Phase Transitions, Membrane-Less Organelles, And Intrinsic Disorder, Vladimir N. Uversky Jan 2019

Supramolecular Fuzziness Of Intracellular Liquid Droplets: Liquid–Liquid Phase Transitions, Membrane-Less Organelles, And Intrinsic Disorder, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Cells are inhomogeneously crowded, possessing a wide range of intracellular liquid droplets abundantly present in the cytoplasm of eukaryotic and bacterial cells, in the mitochondrial matrix and nucleoplasm of eukaryotes, and in the chloroplast’s stroma of plant cells. These proteinaceous membrane-less organelles (PMLOs) not only represent a natural method of intracellular compartmentalization, which is crucial for successful execution of various biological functions, but also serve as important means for the processing of local information and rapid response to the fluctuations in environmental conditions. Since PMLOs, being complex macromolecular assemblages, possess many characteristic features of liquids, they represent highly dynamic (or …


Intrinsic Disorder Of The Baf Complex: Roles In Chromatin Remodeling And Disease Development, Nashwa El Hadidy, Vladimir N. Uversky Jan 2019

Intrinsic Disorder Of The Baf Complex: Roles In Chromatin Remodeling And Disease Development, Nashwa El Hadidy, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The two-meter-long DNA is compressed into chromatin in the nucleus of every cell, which serves as a significant barrier to transcription. Therefore, for processes such as replication and transcription to occur, the highly compacted chromatin must be relaxed, and the processes required for chromatin reorganization for the aim of replication or transcription are controlled by ATP-dependent nucleosome remodelers. One of the most highly studied remodelers of this kind is the BRG1- or BRM-associated factor complex (BAF complex, also known as SWItch/sucrose non-fermentable (SWI/SNF) complex), which is crucial for the regulation of gene expression and differentiation in eukaryotes. Chromatin remodeling complex …


Structure Determination By Single-Particle Cryo-Electron Microscopy: Only The Sky (And Intrinsic Disorder) Is The Limit, Emeka Nwanochie, Vladimir N. Uversky Jan 2019

Structure Determination By Single-Particle Cryo-Electron Microscopy: Only The Sky (And Intrinsic Disorder) Is The Limit, Emeka Nwanochie, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Traditionally, X-ray crystallography and NMR spectroscopy represent major workhorses of structural biologists, with the lion share of protein structures reported in protein data bank (PDB) being generated by these powerful techniques. Despite their wide utilization in protein structure determination, these two techniques have logical limitations, with X-ray crystallography being unsuitable for the analysis of highly dynamic structures and with NMR spectroscopy being restricted to the analysis of relatively small proteins. In recent years, we have witnessed an explosive development of the techniques based on Cryo-electron microscopy (Cryo-EM) for structural characterization of biological molecules. In fact, single-particle Cryo-EM is a special …