CoChat
Sign Up
Cited by 14Protein Structure and DynamicsHeat shock proteins researchBacterial Genetics and Biotechnology

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Hfq C-terminal region forms a β-rich amyloid-like motif without perturbing the N-terminal Sm-like structure

Open access
Berbon, Mélanie, Martinez, Denis, Morvan, Estelle, Grélard, Axelle, Kauffmann, Brice, Waeytens, Jehan, Wien, Frank, Arluison, Véronique, Habenstein, Birgit·2023·Communications Biology
DOI 10.1038/s42003-023-05462-1PMC PMC10590398

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Hfq is a pleitropic actor that serves as stress response and virulence factor in the bacterial cell. To execute its multiple functions, Hfq assembles into symmetric torus-shaped hexamers. Extending outward from the hexameric core, Hfq presents a C-terminal region, described as intrinsically disordered in solution. Many aspects of the role and the structure of this region remain unclear. For instance, in its truncated form it can promote amyloid-like filament assembly. Here, we show that a minimal 11-residue motif at the C-terminal end of Hfq assembles into filaments with amyloid characteristics. Our data suggest that the full-length Hfq in its filamentous state contains a similar molecular fingerprint than that of the short β-strand peptide, and that the Sm-core structure is not affected by filament formation. Hfq proteins might thus co-exist in two forms in vivo, either as isolated, soluble hexamers or as self-assembled hexamers through amyloid-reminiscent interactions, modulating Hfq cellular functions.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s42003-023-05462-1

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 67

  1. Sun, X. Predicted structure and phyletic distribution of the RNA-binding protein Hfq. Nucleic Acids Res. 30, 3662–3671 (2002). · DOI
  2. Gottesman, S. Trouble is coming: signaling pathways that regulate general stress responses in bacteria. J. Biol. Chem. 294, 11685–11700 (2019). · DOI
  3. Valentin-Hansen, P., Eriksen, M. & Udesen, C. The bacterial Sm-like protein Hfq: a key player in RNA transactions: Hfq, an Sm-related protein. Mol. Microbiol. 51, 1525–1533 (2004). · DOI
  4. Wilusz, C. J. & Wilusz, J. Lsm proteins and Hfq: Life at the 3′ end. RNA Biol. 10, 592–601 (2013). · DOI
  5. Schumacher, M. A. Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein. EMBO J. 21, 3546–3556 (2002). · DOI
  6. Link, T. M., Valentin-Hansen, P. & Brennan, R. G. Structure of Escherichia coli Hfq bound to polyriboadenylate RNA. Proc. Natl Acad. Sci. USA 106, 19292–19297 (2009). · DOI
  7. Zhang, A., Schu, D. J., Tjaden, B. C., Storz, G. & Gottesman, S. Mutations in interaction surfaces differentially impact E. coli Hfq association with small RNAs and their mRNA targets. J. Mol. Biol. 425, 3678–3697 (2013). · DOI
  8. Sauer, E., Schmidt, S. & Weichenrieder, O. Small RNA binding to the lateral surface of Hfq hexamers and structural rearrangements upon mRNA target recognition. Proc. Natl Acad. Sci. USA 109, 9396–9401 (2012). · DOI
  9. Beich-Frandsen, M. et al. Structural insights into the dynamics and function of the C-terminus of the E. coli RNA chaperone Hfq. Nucleic Acids Res. 39, 4900–4915 (2011). · DOI
  10. Sauer, E. Structure and RNA-binding properties of the bacterial LSm protein Hfq. RNA Biol. 10, 610–618 (2013). · DOI
  11. Orans, J., Kovach, A. R., Hoff, K. E., Horstmann, N. M. & Brennan, R. G. Crystal structure of an Escherichia coli Hfq Core (residues 2–69)–DNA complex reveals multifunctional nucleic acid binding sites. Nucleic Acids Res. 48, 3987–3997 (2020). · DOI
  12. Dimastrogiovanni, D. et al. Recognition of the small regulatory RNA RydC by the bacterial Hfq protein. eLife 3, e05375 (2014). · DOI
  13. Arluison, V. et al. The C-terminal domain of Escherichia coli Hfq increases the stability of the hexamer: the role of the C-terminal domain on Hfq. Eur. J. Biochem. 271, 1258–1265 (2004). · DOI
  14. Santiago-Frangos, A., Kavita, K., Schu, D. J., Gottesman, S. & Woodson, S. A. C-terminal domain of the RNA chaperone Hfq drives sRNA competition and release of target RNA. Proc. Natl. Acad. Sci. USA 113, E6089–E6096 (2016). · DOI
  15. Turbant, F., Wu, P., Wien, F. & Arluison, V. The amyloid region of Hfq riboregulator promotes DsrA:rpoS RNAs annealing. Biology 10, 900 (2021). · DOI
  16. Parekh, V. J. et al. Crucial role of the C-terminal domain of Hfq protein in genomic instability. Microorganisms 8, 1598 (2020). · DOI
  17. Cech, G. M. et al. The Escherichia coli Hfq protein: an unattended DNA-transactions regulator. Front. Mol. Biosci. 3, 36 (2016). · DOI
  18. Malabirade, A. et al. Revised role for Hfq bacterial regulator on DNA topology. Sci. Rep. 8, 16792 (2018). · DOI
  19. Kubiak, K. et al. Amyloid-like Hfq interaction with single-stranded DNA: involvement in recombination and replication in Escherichia coli. QRB Discov. 3, e15 (2022). · DOI
  20. Cossa, A. et al. Cryo soft X-ray tomography to explore Escherichia coli nucleoid remodeling by Hfq master regulator. J. Struct. Biol. 214, 107912 (2022). · DOI
  21. Malabirade, A. et al. Membrane association of the bacterial riboregulator Hfq and functional perspectives. Sci. Rep. 7, 10724 (2017).
  22. Turbant, F. et al. Unraveling membrane perturbations caused by the bacterial riboregulator Hfq. IJMS 23, 8739 (2022). · DOI
  23. Arluison, V. et al. Three-dimensional structures of fibrillar Sm proteins: Hfq and other Sm-like proteins. J. Mol. Biol. 356, 86–96 (2006). · DOI
  24. Sawaya, M. R., Hughes, M. P., Rodriguez, J. A., Riek, R. & Eisenberg, D. S. The expanding amyloid family: structure, stability, function, and pathogenesis. Cell 184, 4857–4873 (2021). · DOI · Paper page
  25. Nguyen, P. H. et al. Amyloid oligomers: a joint experimental/computational perspective on Alzheimer’s disease, Parkinson’s disease, type II diabetes, and amyotrophic lateral sclerosis. Chem. Rev. 121, 2545–2647 (2021). · DOI
  26. Ke, P. C. et al. Half a century of amyloids: past, present and future. Chem. Soc. Rev. 49, 5473–5509 (2020). · DOI
  27. Turbant, F. et al. Identification and characterization of the Hfq bacterial amyloid region DNA interactions. BBA Adv. 1, 100029 (2021). · DOI
  28. van der Wel, P. C. A. Insights into protein misfolding and aggregation enabled by solid-state NMR spectroscopy. Solid State Nucl. Magn. Reson. 88, 1–14 (2017). · DOI
  29. Loquet, A. et al. 3D structure determination of amyloid fibrils using solid-state NMR spectroscopy. Methods 138–139, 26–38 (2018). · DOI
  30. Habenstein, B. & Loquet, A. Solid-state NMR: an emerging technique in structural biology of self-assemblies. Biophys. Chem. 210, 14–26 (2016). · DOI
  31. Jaroniec, C. P. Two decades of progress in structural and dynamic studies of amyloids by solid-state NMR. J. Magn. Reson. 306, 42–47 (2019). · DOI
  32. Meier, B. H., Riek, R. & Böckmann, A. Emerging structural understanding of amyloid fibrils by solid-state NMR. Trends Biochem. Sci. 42, 777–787 (2017). · DOI
  33. Makin, O. S., Atkins, E., Sikorski, P., Johansson, J. & Serpell, L. C. Molecular basis for amyloid fibril formation and stability. Proc. Natl Acad. Sci. USA 102, 315–320 (2005). · DOI
  34. Nelson, R. et al. Structure of the cross-β spine of amyloid-like fibrils. Nature 435, 773–778 (2005). · DOI
  35. Sunde, M. & Blake, C. C. F. From the globular to the fibrous state: protein structure and structural conversion in amyloid formation. Quart. Rev. Biophys. 31, 1–39 (1998). · DOI
  36. Nguyen, J. T. et al. X-ray diffraction of scrapie prion rods and PrP peptides. J. Mol. Biol. 252, 412–422 (1995). · DOI
  37. Serpell, L. C. Alzheimer’s amyloid fibrils: structure and assembly. Biochim. Biophys Acta 1502, 16–30 (2000). · DOI
  38. Balbirnie, M., Grothe, R. & Eisenberg, D. S. An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated β-sheet structure for amyloid. Proc. Natl Acad. Sci. USA 98, 2375–2380 (2001). · DOI
  39. Eanes, E. D. & Glenner, G. G. X-ray diffraction studies on amyloid filaments. J. Histochem. Cytochem. 16, 673–677 (1968). · DOI
  40. Sikorski, P. & Atkins, E. New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils. Biomacromolecules 6, 425–432 (2005). · DOI
  41. Fraser, P. E. et al. Fibril formation by primate, rodent, and Dutch-hemorrhagic analogs of Alzheimer amyloid .beta.-protein. Biochemistry 31, 10716–10723 (1992). · DOI
  42. Meersman, F., Cabrera, R. Q., McMillan, P. F. & Dmitriev, V. Structural and mechanical properties of TTR105-115 amyloid fibrils from compression experiments. Biophys. J. 100, 193–197 (2011). · DOI
  43. Wang, Y. & Jardetzky, O. Probability-based protein secondary structure identification using combined NMR chemical-shift data. Protein Sci. 11, 852–861 (2002). · DOI
  44. Ruysschaert, J.-M. & Raussens, V. ATR-FTIR Analysis of Amyloid Proteins. in Peptide Self-Assembly (eds Nilsson, B. L. & Doran, T. M.) vol. 1777 69–81 (Springer New York, 2018). · DOI
  45. Waeytens, J. et al. Probing amyloid fibril secondary structures by infrared nanospectroscopy: experimental and theoretical considerations. Analyst 146, 132–145 (2021). · DOI
  46. Cerf, E. et al. Antiparallel β-sheet: a signature structure of the oligomeric amyloid β-peptide. Biochem. J. 421, 415–423 (2009). · DOI
  47. Sarroukh, R. et al. Transformation of amyloid β(1–40) oligomers into fibrils is characterized by a major change in secondary structure. Cell. Mol. Life Sci. 68, 1429–1438 (2011). · DOI
  48. Fortas, E. et al. New insight into the structure and function of Hfq C-terminus. Biosci. Rep. 35, e00190 (2015). · DOI
  49. Shen, Y. & Bax, A. Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology. J. Biomol. NMR 38, 289–302 (2007). · DOI
  50. Azam, T. A. & Ishihama, A. Twelve species of the nucleoid-associated protein from Escherichia coli. J. Biol. Chem. 274, 33105–33113 (1999). · DOI
  51. Diestra, E., Cayrol, B., Arluison, V. & Risco, C. Cellular electron microscopy imaging reveals the localization of the Hfq protein close to the bacterial membrane. PLoS ONE 4, e8301 (2009). · DOI
  52. Turbant, F. et al. Interactions and Insertion of Escherichia coli Hfq into outer membrane vesicles as revealed by infrared and orientated circular dichroism spectroscopies. Int. J. Mol. Sci. 11424 (2023). · DOI
  53. Beaufay, F. et al. Polyphosphate drives bacterial heterochromatin formation. Sci. Adv. 7, eabk0233 (2021). · DOI
  54. Goldberger, O., Szoke, T., Nussbaum-Shochat, A. & Amster-Choder, O. Heterotypic phase separation of Hfq is linked to its roles as an RNA chaperone. Cell Rep. 41, 111881 (2022). · DOI
  55. Santiago-Frangos, A., Jeliazkov, J. R., Gray, J. J. & Woodson, S. A. Acidic C-terminal domains autoregulate the RNA chaperone Hfq. eLife 6, e27049 (2017). · DOI
  56. Sauter, C. Sm-like proteins in Eubacteria: the crystal structure of the Hfq protein from Escherichia coli. Nucleic Acids Res. 31, 4091–4098 (2003). · DOI
  57. De Meutter, J. & Goormaghtigh, E. Protein structural denaturation evaluated by MCR-ALS of protein microarray FTIR spectra. Anal. Chem. 93, 13441–13449 (2021). · DOI
  58. Partouche, D. et al. In situ characterization of Hfq bacterial amyloid: a Fourier-transform infrared spectroscopy study. Pathogens 8, 36 (2019). · DOI
  59. Schmidt, A., Annamalai, K., Schmidt, M., Grigorieff, N. & Fändrich, M. Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril. Proc. Natl Acad. Sci. USA 113, 6200–6205 (2016). · DOI
  60. Sawaya, M. R. et al. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447, 453–457 (2007). · DOI
  61. Sarni, S. H. et al. Intrinsically disordered interaction network in an RNA chaperone revealed by native mass spectrometry. Proc. Natl Acad. Sci. USA 119, e2208780119 (2022). · DOI
  62. Yamaguchi, K. et al. Polyphosphates induce amyloid fibril formation of α-synuclein in concentration-dependent distinct manners. J. Biol. Chem. 296, 100510 (2021). · DOI
  63. Cremers, C. M. et al. Polyphosphate: a conserved modifier of amyloidogenic processes. Mol. Cell 63, 768–780 (2016). · DOI
  64. Obregon, K. A., Hoch, C. T. & Sukhodolets, M. V. Sm-like protein Hfq: composition of the native complex, modifications, and interactions. Biochim. Biophys. Acta 1854, 950–966 (2015). · DOI
  65. Partouche, D. et al. Epigallocatechin gallate remodelling of Hfq amyloid-like region affects Escherichia coli survival. Pathogens 7, 95 (2018). · DOI
  66. Micsonai, A. et al. BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra. Nucleic Acids Res. 46, W315–W322 (2018). · DOI
  67. Elena, B., Lesage, A., Steuernagel, S., Böckmann, A. & Emsley, L. Proton to carbon-13 INEPT in solid-state NMR spectroscopy. J. Am. Chem. Soc. 127, 17296–17302 (2005). · DOI

Metadata

Authors
Berbon, M., Martinez, D., Morvan, E., Grélard, A., Kauffmann, B., Waeytens, J., Wien, F., Arluison, V., & Habenstein, B.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Université Libre de Bruxelles (BE)
  • Synchrotron SOLEIL (FR)
Corresponding author
  • Arluison, Véronique
  • Habenstein, Birgit
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2023-10-21
Volume
6
Issue
1
Pages
1075-1075
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-023-05462-1
PMC
PMC10590398
OpenAlex
W4387844150
Cited by
14
References
1
Citations by year
2026: 2 · 2025: 7 · 2024: 5
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
Funders
  • Society for Research in Child Development
  • Agence Nationale de la Recherche (ANR-19-CE13-0021, 2017-, ANR‐19, ANR18, ANR-18-IDEX-0001)
  • Institut National de la Santé et de la Recherche Médicale (US001, ANR-18-IDEX-0001)
  • Centre National de la Recherche Scientifique (FR 2054)
  • Université de Bordeaux
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Hfq, C-terminal region, hexameric assembly, intrinsically disordered regions, bacterial stress response, virulence factors, protein self-assembly
MeSH terms
Escherichia coli, Protein Binding, Amyloid beta-Peptides, Escherichia coli Proteins, Host Factor 1 Protein

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review