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Peer-reviewedCC BY 4.0Nucleic Acids Research

Reversible autoinhibition of the bacterial replication-licensing Hda–β clamp complex

  • Xuguang Jiang1
  • Radostin Danev1
  • Yanbin Luan1
  • Makoto Nakakido2,3
  • Kouhei Tsumoto2,3,4,5
  • Masahide Kikkawa1
5 affiliations
  1. 1Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo , Bunkyo, Tokyo 113-0033 ,
  2. 2Department of Bioengineering, School of Engineering, The University of Tokyo , Bunkyo, Tokyo 113-8656 ,
  3. 3Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , Bunkyo, Tokyo 113-8656 ,
  4. 4Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo , Bunkyo, Tokyo 113-8655 ,
  5. 5The Institute of Medical Science, The University of Tokyo , Bunkyo, Tokyo 108-8639 ,
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Abstract

Bacterial DNA replication must be tightly controlled to ensure once-per-cell-cycle initiation, requiring precise regulation of the initiator DnaA. The conserved RIDA pathway inactivates DnaA through the Hda–β sliding clamp (DnaN) complex, yet how this system is dynamically regulated has remained unclear. Here, we show that the Hda–DnaN complex exists as a concentration-dependent oligomeric ensemble rather than a static assembly. Using cryo-electron microscopy and mass photometry, we resolve multiple structural states, including an autoinhibited hetero-octamer, a hetero-hexamer intermediate, and a RIDA-compatible hetero-trimer. Structural comparison of these states suggests a plausible route of oligomeric interconversion involving progressive destabilization of Hda self-association, accompanied by exposure of the catalytic arginine finger required for DnaA inactivation. We further propose that this equilibrium operates as a titration-like mechanism that converts local protein concentration into functional states. Together, our findings establish reversible oligomerization as a potential regulatory principle for bacterial replication licensing.

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Cite

BibTeXRIS
BibTeX
@article{jiang2026reversible,
  title = {{Reversible autoinhibition of the bacterial replication-licensing Hda–β clamp complex}},
  author = {Xuguang Jiang and Radostin Danev and Yanbin Luan and Makoto Nakakido and Kouhei Tsumoto and Masahide Kikkawa},
  journal = {Nucleic Acids Research},
  year = {2026},
  month = oct,
  doi = {10.1093/nar/gkag1010},
  url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1010/8986691},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Reversible autoinhibition of the bacterial replication-licensing Hda–β clamp complex
AU  - Xuguang Jiang
AU  - Radostin Danev
AU  - Yanbin Luan
AU  - Makoto Nakakido
AU  - Kouhei Tsumoto
AU  - Masahide Kikkawa
PY  - 2026
DA  - 2026/10/23
JO  - Nucleic Acids Research
DO  - 10.1093/nar/gkag1010
UR  - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1010/8986691
AB  - Bacterial DNA replication must be tightly controlled to ensure once-per-cell-cycle initiation, requiring precise regulation of the initiator DnaA. The conserved RIDA pathway inactivates DnaA through the Hda–β sliding clamp (DnaN) complex, yet how this system is dynamically regulated has remained unclear. Here, we show that the Hda–DnaN complex exists as a concentration-dependent oligomeric ensemble rather than a static assembly. Using cryo-electron microscopy and mass photometry, we resolve multiple structural states, including an autoinhibited hetero-octamer, a hetero-hexamer intermediate, and a RIDA-compatible hetero-trimer. Structural comparison of these states suggests a plausible route of oligomeric interconversion involving progressive destabilization of Hda self-association, accompanied by exposure of the catalytic arginine finger required for DnaA inactivation. We further propose that this equilibrium operates as a titration-like mechanism that converts local protein concentration into functional states. Together, our findings establish reversible oligomerization as a potential regulatory principle for bacterial replication licensing.
SN  - 0305-1048
SN  - 1362-4962
ER  -