CoChat
Sign Up
PreprintCited by 17CRISPR and Genetic EngineeringBacterial Genetics and BiotechnologyBacteriophages and microbial interactions

The DOI matches its Crossref record; its reference list is not available.

Filament formation activates protease and ring nuclease activities of CRISPR SAVED-Lon

Open access
Smalakyte, Dalia, Ruksenaite, Audrone, Sasnauskas, Giedrius, Tamulaitiene, Giedre, Tamulaitis, Gintautas·2024·Molecular Cell
DOI 10.1101/2024.05.08.593097

Preprint — published as 10.1016/j.molcel.2024.09.002 · Paper page

Open this paper in CoChat — free account

Abstract

SUMMARY: To combat phage infection, type III CRISPR-Cas systems utilize cyclic oligoadenylates (cA n ) signaling to activate various auxiliary effectors, including the CRISPR-associated SAVED-Lon protease CalpL, which forms a tripartite effector system together with an anti-σ factor, CalpT, and an ECF-like σ factor, CalpS. Here we report the characterization of the Candidatus Cloacimonas acidaminovorans CalpL-CalpT-CalpS. We demonstrate that cA 4 binding triggers CalpL filament formation and activates it to cleave CalpT within the CalpT-CalpS dimer. This cleavage exposes the CalpT C-degron, which targets it for further degradation by cellular proteases. Consequently, CalpS is released to bind to RNA polymerase, causing growth arrest in E. coli . Furthermore, the CalpL-CalpT-CalpS system is regulated by the SAVED domain of CalpL, which is a ring nuclease that cleaves cA 4 in a sequential three-step mechanism. These findings provide key mechanistic details for the activation, proteolytic events, and regulation of the signaling cascade in the type III CRISPR-Cas immunity.

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 · 10.1101/2024.05.08.593097

Cites

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

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 93 · Cited by 17

Research works printed but not linked: 75

  1. 10.1146/annurev-genet-022120-112523 · DOI
  2. 10.1016/j.tibs.2023.10.006 · DOI
  3. 10.1126/science.aao0100 · DOI · Paper page
  4. 10.1038/nature23467 · DOI · Paper page
  5. 10.1093/nar/gkaa635 · DOI
  6. 10.1093/nar/gkaa176 · DOI
  7. 10.1038/s41467-019-14222-x · DOI
  8. 10.1038/s41586-021-03206-x · DOI
  9. 10.1093/nar/gkab073 · DOI
  10. 10.3390/biom11121852 · DOI
  11. 10.1126/science.adj2107 · DOI
  12. 10.1038/s41586-023-06902-y · DOI
  13. 10.1093/nar/gkae167 · DOI · Paper page
  14. 10.1128/JB.00365-20 · DOI
  15. 10.1146/annurev-virology-111821-115636 · DOI
  16. 10.1038/s41586-022-05571-7 · DOI · Paper page
  17. 10.1146/annurev-biochem-062917-012848 · DOI
  18. 10.1126/science.abk2718 · DOI
  19. 10.1126/science.add7450 · DOI
  20. 10.1016/j.mib.2013.02.001 · DOI
  21. 10.1126/science.add5064 · DOI
  22. 10.7554/eLife.36734 · DOI
  23. 10.1146/annurev-virology-100120-010228 · DOI
  24. 10.1038/s41586-018-0557-5 · DOI
  25. 10.7554/eLife.57627 · DOI
  26. 10.1093/nar/gkaa634 · DOI
  27. 10.1016/j.jmb.2019.04.041 · DOI
  28. 10.1038/s41467-020-15334-5 · DOI
  29. 10.1016/j.molcel.2019.06.014 · DOI
  30. 10.1093/nar/gkaa298 · DOI
  31. 10.1101/2023.11.24.568546 · DOI
  32. 10.1093/nar/gkab1190 · DOI
  33. 10.1038/s41586-022-05070-9 · DOI · Paper page
  34. 10.1016/j.cell.2020.05.019 · DOI
  35. 10.1093/nar/gkz470 · DOI
  36. 10.1073/pnas.1816596116 · DOI · Paper page
  37. 10.7554/eLife.61496 · DOI
  38. 10.7554/eLife.52774 · DOI
  39. 10.1016/S1097-2765(03)00060-1 · DOI
  40. 10.1016/j.cell.2019.05.002 · DOI
  41. 10.1126/science.271.5251.990 · DOI · Paper page
  42. 10.1073/pnas.191375298 · DOI
  43. 10.1146/annurev.micro.112408.134219 · DOI
  44. 10.1101/gad.1240104 · DOI
  45. 10.1016/S1097-2765(03)00148-5 · DOI
  46. 10.1101/gad.1002302 · DOI
  47. 10.1093/nar/gkad101 · DOI
  48. 10.1093/nar/gkab1130 · DOI
  49. 10.1093/nar/gkac923 · DOI
  50. 10.1038/s41586-019-1909-5 · DOI
  51. 10.1074/jbc.RA120.014099 · DOI
  52. 10.1080/15476286.2015.1051300 · DOI
  53. 10.1126/science.adk0378 · DOI
  54. 10.1038/s41467-021-26738-2 · DOI
  55. 10.1038/s41594-024-01220-x · DOI
  56. 10.1038/s41586-020-2719-5 · DOI
  57. 10.1016/j.cell.2021.09.031 · DOI
  58. 10.1038/s41586-024-07092-x · DOI
  59. 10.1016/j.celrep.2023.112672 · DOI
  60. 10.1016/j.jmb.2017.12.007 · DOI · Paper page
  61. 10.1002/pro.4519 · DOI
  62. 10.1101/2021.10.04.463034 · DOI · Paper page
  63. 10.1038/s41592-022-01488-1 · DOI · Paper page
  64. 10.1016/0378-1119(95)00685-0 · DOI
  65. 10.1093/protein/14.12.993 · DOI
  66. 10.1089/crispr.2020.0032 · DOI
  67. 10.1038/ncomms11293 · DOI
  68. 10.1038/nmeth.4169 · DOI · Paper page
  69. 10.1038/s41592-020-00990-8 · DOI
  70. 10.1038/nmeth.4347 · DOI
  71. 10.1016/j.jmb.2003.07.013 · DOI · Paper page
  72. 10.1107/S0907444910007493 · DOI · Paper page
  73. 10.1107/S2059798319011471 · DOI · Paper page
  74. 10.1002/pro.3943 · DOI
  75. 10.1007/s001800200117 · DOI

Metadata

Authors
Smalakyte, D., Ruksenaite, A., Sasnauskas, G., Tamulaitiene, G., & Tamulaitis, G.
Affiliations
Vilnius University (LT)
Corresponding author
Tamulaitis, Gintautas
ORCID
Venue
Molecular Cell
Publisher
openRxiv
Published
2024-05-08
Volume
84
Issue
21
Pages
4239-4255.e8
ISSN
1097-2765 (ISSN-L)
DOI
10.1101/2024.05.08.593097
OpenAlex
W4403065814
Cited by
17
References
93
Citations by year
2026: 6 · 2025: 10 · 2024: 1
FWCI
2.32
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Lietuvos Mokslo Taryba (S-MIP-22-09)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
Keywords
type III CRISPR-Cas, CALP, cyclic oligoadenylate, filamentation, anti-sigma factor, ECF sigma factor, phage immunity, RNA polymerase binding, growth arrest
MeSH terms
Bacterial Proteins, Escherichia coli, Protein Binding, Sigma Factor, Signal Transduction, Gene Expression Regulation, Bacterial, Proteolysis, CRISPR-Cas Systems, CRISPR-Associated Proteins

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