Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy

  • Akihito Nishiyama
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Masahiro Shimizu
    Nano Life Science Institute, Kanazawa University , Kakumamachi,  Kanazawa , Ishikawa  920-1192 , Japan
  • Tomoyuki Narita
    Nano Life Science Institute, Kanazawa University , Kakumamachi,  Kanazawa , Ishikawa  920-1192 , Japan
  • Noriyuki Kodera
    Nano Life Science Institute, Kanazawa University , Kakumamachi,  Kanazawa , Ishikawa  920-1192 , Japan
  • Yuriko Ozeki
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Akira Yokoyama
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Kouta Mayanagi
    Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka  812-8582 , Japan
  • Takehiro Yamaguchi
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Mariko Hakamata
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Amina Kaboso Shaban
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Yoshitaka Tateishi
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan
  • Kosuke Ito
    Graduate School of Science and Technology, Niigata University , 2-8050 Ikarashi , Nishi-ku , Niigata  950-2181 , Japan
  • Sohkichi Matsumoto
    Department of Bacteriology, Niigata University School of Medicine , 1-757 Asahimachi-dori , Chuo-ku , Niigata  951-8510 , Japan

書誌事項

公開日
2023-12-04
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by-nc/4.0/
DOI
  • 10.1093/nar/gkad1149
公開者
Oxford University Press (OUP)

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説明

<jats:title>Abstract</jats:title> <jats:p>Mycobacteria are the major human pathogens with the capacity to become dormant persisters. Mycobacterial DNA-binding protein 1 (MDP1), an abundant histone-like protein in dormant mycobacteria, induces dormancy phenotypes, e.g. chromosome compaction and growth suppression. For these functions, the polycationic intrinsically disordered region (IDR) is essential. However, the disordered property of IDR stands in the way of clarifying the molecular mechanism. Here we clarified the molecular and structural mechanism of DNA compaction by MDP1. Using high-speed atomic force microscopy, we observed that monomeric MDP1 bundles two adjacent DNA duplexes side-by-side via IDR. Combined with coarse-grained molecular dynamics simulation, we revealed the novel dynamic DNA cross-linking model of MDP1 in which a stretched IDR cross-links two DNA duplexes like double-sided tape. IDR is able to hijack HU function, resulting in the induction of strong mycobacterial growth arrest. This IDR-mediated reversible DNA cross-linking is a reasonable model for MDP1 suppression of the genomic function in the resuscitable non-replicating dormant mycobacteria.</jats:p>

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