Molecular Dynamics Simulations Reveal Novel Interacting Regions of Human Prion Protein to Brucella abortus Hsp60 Protein.

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    • Source:
      Publisher: Springer Country of Publication: Switzerland NLM ID: 9423533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0305 (Electronic) Linking ISSN: 10736085 NLM ISO Abbreviation: Mol Biotechnol Subsets: MEDLINE
    • Publication Information:
      Publication: [Cham] : Springer
      Original Publication: Totowa, NJ : Humana Press, c1994-
    • Subject Terms:
    • Abstract:
      The distinctive morphology characteristics of microfold cells (M cells) allow the vaccine antigen not only to interact with immune cells directly, but also to effectively stimulate mucosal immune responses via receptors on its apical surface. Human prion protein, a transmembrane receptor for Brucella abortus Hsp60, is highly expressed on the M cell surface. Nonetheless, this protein tends to express in inclusion body in prokaryotic hosts. In this study, the shorter interacting regions of human prion protein were identified via computational methods such as docking and molecular dynamics simulations to minimize its aggregation tendency. The computational calculations revealed three novel human prion protein-interacting regions, namely PrP125, PrP174, and PrP180. In accordance with in silico prediction, the biologically synthesized peptides fusing with GST tag demonstrated their specific binding to Hsp60 protein via pull-down assay. Hence, this finding laid the groundwork for M-cell targeting candidate validation through these newly identified interacting regions.
      (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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    • Contributed Indexing:
      Keywords: Homology modeling; Hsp60 protein; Human prion protein; M cell; Molecular docking; Molecular dynamics (MDs); Pull-down assay
    • Accession Number:
      0 (Bacterial Proteins)
      0 (Chaperonin 60)
      0 (Prion Proteins)
    • Publication Date:
      Date Created: 20230112 Date Completed: 20240424 Latest Revision: 20240507
    • Publication Date:
      20240507
    • Accession Number:
      PMC9838441
    • Accession Number:
      10.1007/s12033-023-00655-9
    • Accession Number:
      36633832