Amyloid-like DNA bridging: a new mode of DNA shaping
All organisms depend on specific proteins to compact and organize their genomes. In eukaryotes, histones fulfil this role, while bacterial chromosomes are shaped by nucleoid-associated proteins (NAPs). Among its pleiotropic functions, the NAP Hfq plays a pivotal role in bacterial genome organization. In this study, we characterized the structure of the C-terminal extension of Hfq, which mediates chromosomal compaction, in its DNA-bound state. Using an integrative approach that combined transmission electron microscopy, neutron scattering, site-directed mutagenesis, and molecular modeling, we identified an amyloid module formed by the C-terminal region of Hfq. This module uniquely bridges and compacts six DNA molecules, marking the first documented instance of an amyloid structure with DNA-bridging properties. Our findings redefine the functional landscape of amyloids, linking them to genome architecture and gene regulation. This result suggests that amyloid-DNA interactions may represent a conserved mechanism across biological systems, with profound implications for understanding genome organization and the regulation of gene expression in both prokaryotes and eukaryotes.
Authors
- Judith Peters (ORCID: https://orcid.org/0000-0001-5151-7710)
- Marisela Vélez (ORCID: https://orcid.org/0000-0002-9424-510X)
- Svemir Rudić (ORCID: https://orcid.org/0000-0003-3023-8565)
- Tatsuhito Matsuo (ORCID: https://orcid.org/0000-0001-7256-3206)
- Marcos Gragera (ORCID: https://orcid.org/0000-0002-3097-1743)
- M. Teresa Bueno-Carrasco (ORCID: https://orcid.org/0000-0003-1586-2589)
- Anne Martel (ORCID: https://orcid.org/0000-0002-1232-8519)
- Frank Wien (ORCID: https://orcid.org/0000-0002-0752-8735)
- Véronique Arluison (ORCID: https://orcid.org/0000-0003-4056-7282)
- Rocío Arranz (ORCID: https://orcid.org/0000-0001-5321-0915)
- Johan R. C. van der Maarel (ORCID: https://orcid.org/0000-0001-5560-0298)
- Heloisa N. Bordallo (ORCID: https://orcid.org/0000-0003-0750-0553)
- Antoine Cossa (ORCID: https://orcid.org/0000-0002-8073-8704)
- Gautier Moroy (ORCID: https://orcid.org/0000-0002-8973-0477)
Institutions
- University of Copenhagen (DK)
- Rutherford Appleton Laboratory (GB)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- National University of Singapore (SG)
- Institut Universitaire de France (FR)
- Université Paris Cité (FR)
- Synchrotron soleil (FR)
- Instituto de Catálisis y Petroleoquímica (ES)
- Sorbonne Paris Cité (FR)
- Centro Nacional de Biotecnología (ES)
- Institut Laue-Langevin (FR)
- Laboratoire Léon Brillouin (FR)
- CEA Paris-Saclay (FR)
- Hiroshima International University (JP)
- Unit of Functional and Adaptive Biology (FR)
- Marie Curie (GB)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-02-27
- DOI
- https://doi.org/10.1093/nar/gkaf169
- Citations
- 11
- Primary Topic
- Bacterial Genetics and Biotechnology
- Type
- article
- Field-Weighted Citation Impact
- 19.99
Funders
- Sanofi
- European Commission
- Agence Nationale de la Recherche
- Monash University
- Ministry of Education, India
- Science and Technology Facilities Council
- Centro Nacional de Biotecnología