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Structure, dynamics, and stability of the smallest and most complex 71 protein knot

Hsu, Min-Feng ; Sriramoju, Manoj Kumar ; Lai, Chih-Hsuan ; Chen, Yun-Ru ; Huang, Jing-Siou ; Ko, Tzu-Ping ; Huang, Kai-Fa ; Hsu, Shang-Te Danny

The Journal of biological chemistry, 2024-01, Vol.300 (1), p.105553-105553, Article 105553 [Periódico revisado por pares]

American Society for Biochemistry and Molecular Biology

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  • Título:
    Structure, dynamics, and stability of the smallest and most complex 71 protein knot
  • Autor: Hsu, Min-Feng ; Sriramoju, Manoj Kumar ; Lai, Chih-Hsuan ; Chen, Yun-Ru ; Huang, Jing-Siou ; Ko, Tzu-Ping ; Huang, Kai-Fa ; Hsu, Shang-Te Danny
  • Assuntos: JBC Communication
  • É parte de: The Journal of biological chemistry, 2024-01, Vol.300 (1), p.105553-105553, Article 105553
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    These authors contributed equally to this work.
  • Descrição: Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 71 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus. Q9PR55 is monomeric in solution, making it the smallest and most complex knotted protein known to date. In addition to its exceptional chemical stability against urea-induced unfolding, Q9PR55 is remarkably robust to resist the mechanical unfolding-coupled proteolysis by a bacterial proteasome, ClpXP. Our results suggest that the mechanical resistance against pulling-induced unfolding is determined by the complexity of the knotted topology rather than the size of the molecule.
  • Editor: American Society for Biochemistry and Molecular Biology
  • Idioma: Inglês

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