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Full-Text Articles in Medicine and Health Sciences
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 …
Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp
Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp
Molecular Medicine Faculty Publications
Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.