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Full-Text Articles in Medicine and Health Sciences
Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Molecular Medicine Faculty Publications
Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in …
Potential Molecular Mechanisms Of Rare Anti-Tumor Immune Response By Sars-Cov-2 In Isolated Cases Of Lymphomas, Debmalya Barh, Sandeep Tiwary, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky
Potential Molecular Mechanisms Of Rare Anti-Tumor Immune Response By Sars-Cov-2 In Isolated Cases Of Lymphomas, Debmalya Barh, Sandeep Tiwary, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex …
The Participation Of The Intrinsically Disordered Regions Of The Bhlh-Pas Transcription Factors In Disease Development, Marta Kolonko-Adamska, Vladimir N. Uversky, Beata Greb-Markiewicz
The Participation Of The Intrinsically Disordered Regions Of The Bhlh-Pas Transcription Factors In Disease Development, Marta Kolonko-Adamska, Vladimir N. Uversky, Beata Greb-Markiewicz
Molecular Medicine Faculty Publications
The basic helix–loop–helix/Per-ARNT-SIM (bHLH-PAS) proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, ranging from differentiation and development control by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for regulation of their activity. Our aim was to analyze the potential connection between disordered regions of the bHLH-PAS transcription factors, post-transcriptional modifications and liquid-liquid phase separation, in the context of disease-associated missense mutations. Highly flexible disordered regions, enriched in short motives which …
Interferon Beta Activity Is Modulated Via Binding Of Specific S100 Proteins, Alexei S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Alexander I. Denesyuk, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Interferon Beta Activity Is Modulated Via Binding Of Specific S100 Proteins, Alexei S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Alexander I. Denesyuk, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Molecular Medicine Faculty Publications
Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca2+-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca2+-dependent …
Unstructured Biology Of Proteins From Ubiquitin-Proteasome System: Roles In Cancer And Neurodegenerative Diseases, Kundlik Gadhave, Prateek Kumar, Shivani K. Kapuganti, Vladimir N. Uversky, Rajanish Giri
Unstructured Biology Of Proteins From Ubiquitin-Proteasome System: Roles In Cancer And Neurodegenerative Diseases, Kundlik Gadhave, Prateek Kumar, Shivani K. Kapuganti, Vladimir N. Uversky, Rajanish Giri
Molecular Medicine Faculty Publications
The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of the cellular protein surveillance machinery, and its dysfunction leads to cancer, neurodegenerative and immunological disorders. Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs). The structure–function relationships of UPS components have not been identified completely; therefore, in this study, we have …
Distribution And Cluster Analysis Of Predicted Intrinsically Disordered Protein Pfam Domains, Robert W. Williams, Bin Xue, Vladimir N. Uversky, A. Keith Dunker
Distribution And Cluster Analysis Of Predicted Intrinsically Disordered Protein Pfam Domains, Robert W. Williams, Bin Xue, Vladimir N. Uversky, A. Keith Dunker
Molecular Medicine Faculty Publications
The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members …