The landscape of intrinsically disordered proteins in Leishmania parasite: Implications for drug discovery.

Autor: Gollapalli S; Department of Biotechnology, National Institute of Technology-Warangal, Warangal 506004, Telangana, India., Sooram B; Division of Neurogeriatrics, Karolinska Institutet, Solna, 17 165, Solnavagen, Sweden., Sugandh H; Department of Biotechnology, National Institute of Technology-Warangal, Warangal 506004, Telangana, India., Saudagar P; Department of Biotechnology, National Institute of Technology-Warangal, Warangal 506004, Telangana, India. Electronic address: ps@nitw.ac.in.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec; Vol. 283 (Pt 2), pp. 137290. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.ijbiomac.2024.137290
Abstrakt: Proteins that lack three-dimensional structures are known as Intrinsically disordered proteins (IDPs). In this study, we aimed to identify intrinsically disordered proteins in the Leishmania donovani proteome using various predictors that can identify IDPs based on amino acid residues and charge hydropathy. Top identified IDPs are analyzed using STRING, PSP-Hunter, Deep Loc-2.0, and Alpha fold to understand the protein-protein interaction, phase separation, localization, and structural assessment of those proteins. From this study, we found that >50 % of Leishmania donovani proteome has proteins or regions of proteins that are intrinsically disordered with VSL2 score >0.5; most proteins interact with many other proteins with PPI enrichment p-value <1.0e-16. Few proteins, such as Protein phosphatase inhibitor, UMSBP, and Zinc knuckle, have redox-sensitive regions. Functional disorder profiles of identified IDPs showed MoRFs and predicted protein domains. HASPB, UTP11, Nucleolar protein 12, and UMSBP have a high probability of undergoing phase separation. Localization studies showed that most of these proteins are in the cytoplasm and nucleus. Our present study of identifying IDPs in Leishmania proteome yields significant information on druggable targets and can serve as a basis for further studies to identify unexplored pathways.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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