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Full-Text Articles in Medicine and Health Sciences
Liaisons Dangereuses: Intrinsic Disorder In Cellular Proteins Recruited To Viral Infection-Related Biocondensates, Greta Bianchi, Stefania Brocca, Sonia Longhi, Vladimir N. Uversky
Liaisons Dangereuses: Intrinsic Disorder In Cellular Proteins Recruited To Viral Infection-Related Biocondensates, Greta Bianchi, Stefania Brocca, Sonia Longhi, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Liquid–liquid phase separation (LLPS) is responsible for the formation of so-called membrane-less organelles (MLOs) that are essential for the spatio-temporal organization of the cell. Intrinsically disordered proteins (IDPs) or regions (IDRs), either alone or in conjunction with nucleic acids, are involved in the formation of these intracellular condensates. Notably, viruses exploit LLPS at their own benefit to form viral replication compartments. Beyond giving rise to biomolecular condensates, viral proteins are also known to partition into cellular MLOs, thus raising the question as to whether these cellular phase-separating proteins are drivers of LLPS or behave as clients/regulators. Here, we focus on …
Biomolecular Condensates: Insights Into Early And Late Steps Of The Hiv-1 Replication Cycle, Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland
Biomolecular Condensates: Insights Into Early And Late Steps Of The Hiv-1 Replication Cycle, Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland
Molecular Medicine Faculty Publications
A rapidly evolving understanding of phase separation in the biological and physical sciences has led to the redefining of virus-engineered replication compartments in many viruses with RNA genomes. Condensation of viral, host and genomic and subgenomic RNAs can take place to evade the innate immunity response and to help viral replication. Divergent viruses prompt liquid–liquid phase separation (LLPS) to invade the host cell. During HIV replication there are several steps involving LLPS. In this review, we characterize the ability of individual viral and host partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models of phase separation …
Effect Of Protein–Protein Interactions On Translational Diffusion Of Spheroidal Proteins, Aleksandra M. Kusova, Aleksandr E. Sitnitsky, Vladimir N. Uversky, Yuriy F. Zuev
Effect Of Protein–Protein Interactions On Translational Diffusion Of Spheroidal Proteins, Aleksandra M. Kusova, Aleksandr E. Sitnitsky, Vladimir N. Uversky, Yuriy F. Zuev
Molecular Medicine Faculty Publications
One of the commonly accepted approaches to estimate protein–protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present review article observes a phenomenological approach to analyze PPI effects via concentration dependencies of self- and collective translational diffusion coefficient for several spheroidal proteins derived from the pulsed field gradient NMR (PFG NMR) and dynamic light scattering (DLS), respectively. These proteins are rigid globular α-chymotrypsin (ChTr) and human serum albumin (HSA), and partly disordered α-casein (α-CN) and β-lactoglobulin (β-Lg). The PPI analysis enabled us to reveal the dominance of intermolecular repulsion at low ionic strength of solution …
Hepatitis C Virus Infection And Intrinsic Disorder In The Signaling Pathways Induced By Toll-Like Receptors, Elrashdy M. Redwan, Abdullah A. Aljadawi, Vladimir N. Uversky
Hepatitis C Virus Infection And Intrinsic Disorder In The Signaling Pathways Induced By Toll-Like Receptors, Elrashdy M. Redwan, Abdullah A. Aljadawi, Vladimir N. Uversky
Molecular Medicine Faculty Publications
In this study, we examined the interplay between protein intrinsic disorder, hepatitis C virus (HCV) infection, and signaling pathways induced by Toll-like receptors (TLRs). To this end, 10 HCV proteins, 10 human TLRs, and 41 proteins from the TLR-induced downstream pathways were considered from the prevalence of intrinsic disorder. Mapping of the intrinsic disorder to the HCV-TLR interactome and to the TLR-based pathways of human innate immune response to the HCV infection demonstrates that substantial levels of intrinsic disorder are characteristic for proteins involved in the regulation and execution of these innate immunity pathways and in HCV-TLR interaction. Disordered regions, …
Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky
Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Intrinsically disordered proteins and protein regions (IDPs/IDPRs) are mainly involved in signaling pathways, where fast regulation, temporal interactions, promiscuous interactions, and assemblies of structurally diverse components including membranes are essential. The autophagy pathway builds, de novo, a membrane organelle, the autophagosome, using carefully orchestrated interactions between proteins and lipid bilayers. Here, we discuss molecular mechanisms related to the protein disorder-based interactions of the autophagy machinery with membranes. We describe not only membrane binding phenomenon, but also examples of membrane remodeling processes including membrane tethering, bending, curvature sensing, and/or fragmentation of membrane organelles such as the endoplasmic reticulum, which is an …
The Pathophysiological Significance Of Fibulin-3, Imogen Livingstone, Vladimir N. Uversky, Dominic Furniss, Akira Wiberg
The Pathophysiological Significance Of Fibulin-3, Imogen Livingstone, Vladimir N. Uversky, Dominic Furniss, Akira Wiberg
Molecular Medicine Faculty Publications
Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular …
Zooming Into The Dark Side Of Human Annexin-S100 Complexes: Dynamic Alliance Of Flexible Partners, Judith Weisz, Vladimir N. Uversky
Zooming Into The Dark Side Of Human Annexin-S100 Complexes: Dynamic Alliance Of Flexible Partners, Judith Weisz, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Annexins and S100 proteins form two large families of Ca2+-binding proteins. They are quite different both structurally and functionally, with S100 proteins being small (10–12 kDa) acidic regulatory proteins from the EF-hand superfamily of Ca2+-binding proteins, and with annexins being at least three-fold larger (329 ± 12 versus 98 ± 7 residues) and using non-EF-hand-based mechanism for calcium binding. Members of both families have multiple biological roles, being able to bind to a large cohort of partners and possessing a multitude of functions. Furthermore, annexins and S100 proteins can interact with each other in either a Ca2+-dependent or Ca2+-independent manner, …