Molecular Genomic Insights into Melanoma Associated Proteins PRAME and BAP1

Nawn, D.; Hassan, S. S.; Hromic Jahjefendic, A.; Bhattacharya, T.; Basu, P.; Redwan, E. M.; Barh, D.; Andrade, B.; Aljabali, A. A.; Serrano Aroca, A.; Lundstrom, K.; Tambuwala, M. M.; Uversky, V. N.

doi:10.1101/2024.03.05.583532

bioRxiv · 10.1101/2024.03.05.583532

Molecular Genomic Insights into Melanoma Associated Proteins PRAME and BAP1

Nawn, D.·Hassan, S. S.·Hromic Jahjefendic, A.·Bhattacharya, T.·Basu, P.·Redwan, E. M.·Barh, D.·Andrade, B.·Aljabali, A. A.·Serrano Aroca, A.·Lundstrom, K.·Tambuwala, M. M.·Uversky, V. N.

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Abstract

BackgroundMelanoma, a worldwide widespread skin cancer with over 325,000 yearly incidences, demands a thorough understanding of its molecular components to create effective therapeutics. This study looks at the PRAME (cutaneous melanoma-associated antigen) and BAP1 (gene controlling gene-environment interactions) proteins, which are important in melanoma development and are important for understanding the molecular landscape of melanoma. IntroductionWhile playing a crucial role in melanoma, the structural and functional characteristics of PRAME and BAP1 remain unidentified. This work tries to unravel their complexities by investigating conserved residues, sequence invariance, and other molecular characteristics that contribute to their importance in melanoma. Promising therapeutic targets for melanoma therapy are identified by analyzing these proteins at the molecular level. MethodsThe study makes extensive use of bioinformatics methods to analyze PRAME and BAP1, including sequence conservation, inherent disorder, polyglutamic acid presence, and polarity alterations. Established approaches are used to investigate residue changes and their effects on protein folding, aggregation, and interactions. ResultsPRAME and BAP1 conserved residues highlight their critical roles in protein function and interaction. Sequence invariance indicates the possibility of functional relevance and evolutionary conservation. In intrinsically disordered proteins (IDPRs), PRAME has enhanced intrinsic disorder and flexibility, whereas BAP1 has changed disorder-promoting residue sequences. Polyglutamic acid strings are found in both proteins, emphasizing their modulatory involvement in protein interactions. Protein folding and aggregation are influenced by polarity shifts, with a balanced distribution of acidic and basic residues preserving native structures. The ratios and distributions of amino acids, particularly neutral residues, have a profound influence on interactions and gene dysregulation. ConclusionPRAME and BAP1 structural and functional understanding pave the way for diagnostic and tailored treatment options in melanoma. Differences in residue alterations, polarity distributions, and amino acid ratios provide intriguing drug design options. This research contributes to a better knowledge of melanoma-associated two proteins, opening the path for novel diagnostic and therapy techniques in skin cancer and beyond.

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Nawn, D., Hassan, S. S., Hromic Jahjefendic, A., Bhattacharya, T., Basu, P., Redwan, E. M., Barh, D., Andrade, B., Aljabali, A. A., Serrano Aroca, A., Lundstrom, K., Tambuwala, M. M., Uversky, V. N.. 2024-03-11. Molecular Genomic Insights into Melanoma Associated Proteins PRAME and BAP1. https://doi.org/10.1101/2024.03.05.583532

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