Cyanophage CP12 Rewires Host Carbon Regulation through Interface Remodeling and Redox Buffering

Abstract

Picocyanobacteria drive ocean carbon fixation, and cyanophages reshape host metabolism during infection. In cyanobacteria, the intrinsically disorder Calvin cycle protein 12 (CP12) assembles glyceraldehyde-3-phosphate dehydrogenase (GAP2) and phosphoribulokinase (PRK) into the inhibitory dark complex, yet how phage CP12 homologs modulate redox-sensitive partners remains unclear. Here, we examined viral CP12 across sequence, structure, and post-translational modification (PTM) complexities to resolve the mechanistic remodeling of dark-complex assembly and regulation. Protein-family analysis of CP12 homologs across diverse lineages showed that viral CP12 preserves interface-dominated positions while shifting partner-facing chemistry toward charged and geometry-modulating features. Matched molecular dynamics simulations (MD) of Prochlorococcus MED4 and cyanophage P-HM2 showed that phage CP12 preserves assembly while strengthening PRK-facing contacts and reducing GAP2-facing interface burial. MED4 redox proteomics identified coordinated cysteine oxidation across CP12 and GAP2 under light disturbance, guiding MD to explore thiol-PTM states. Conformational divergence increased with PTM load and localized mainly to GAP2 modifications. Thiol PTM at GAP2 imposed the largest CP12 binding-energy cost, which P-HM2 CP12 buffered, yielding smaller comparative binding-energy penalties than host CP12. These findings link sequence-driven chemistry to interface dynamics and redox PTM responsiveness to light, defining phage CP12 as a regulatory mimetic that may retune host carbon regulation during infection.

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BibTeX RIS

BibTeX

@misc{widmann2026cyanophage,
  title = {{Cyanophage CP12 Rewires Host Carbon Regulation through Interface Remodeling and Redox Buffering}},
  author = {S. Widmann and R. Wu and M. Nelson and D. Mejia-Rodriguez and s. samantray and R. Neff and S. Feng and X. Li and J. Rozum and A. George and P. Rigor and P. Bohutskyi and N. Boise and H. Kim and L. N. Anderson and W.-J. QIAN and E. Olaleye and K. Idowu and A. Andersen and M. S. Cheung},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.10.750766},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750766v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Cyanophage CP12 Rewires Host Carbon Regulation through Interface Remodeling and Redox Buffering
AU  - S. Widmann
AU  - R. Wu
AU  - M. Nelson
AU  - D. Mejia-Rodriguez
AU  - s. samantray
AU  - R. Neff
AU  - S. Feng
AU  - X. Li
AU  - J. Rozum
AU  - A. George
AU  - P. Rigor
AU  - P. Bohutskyi
AU  - N. Boise
AU  - H. Kim
AU  - L. N. Anderson
AU  - W.-J. QIAN
AU  - E. Olaleye
AU  - K. Idowu
AU  - A. Andersen
AU  - M. S. Cheung
PY  - 2026
DA  - 2026/09/10
PB  - bioRxiv
DO  - 10.64898/2026.09.10.750766
UR  - https://www.biorxiv.org/content/10.64898/2026.09.10.750766v1
AB  - Picocyanobacteria drive ocean carbon fixation, and cyanophages reshape host metabolism during infection. In cyanobacteria, the intrinsically disorder Calvin cycle protein 12 (CP12) assembles glyceraldehyde-3-phosphate dehydrogenase (GAP2) and phosphoribulokinase (PRK) into the inhibitory dark complex, yet how phage CP12 homologs modulate redox-sensitive partners remains unclear. Here, we examined viral CP12 across sequence, structure, and post-translational modification (PTM) complexities to resolve the mechanistic remodeling of dark-complex assembly and regulation. Protein-family analysis of CP12 homologs across diverse lineages showed that viral CP12 preserves interface-dominated positions while shifting partner-facing chemistry toward charged and geometry-modulating features. Matched molecular dynamics simulations (MD) of Prochlorococcus MED4 and cyanophage P-HM2 showed that phage CP12 preserves assembly while strengthening PRK-facing contacts and reducing GAP2-facing interface burial. MED4 redox proteomics identified coordinated cysteine oxidation across CP12 and GAP2 under light disturbance, guiding MD to explore thiol-PTM states. Conformational divergence increased with PTM load and localized mainly to GAP2 modifications. Thiol PTM at GAP2 imposed the largest CP12 binding-energy cost, which P-HM2 CP12 buffered, yielding smaller comparative binding-energy penalties than host CP12. These findings link sequence-driven chemistry to interface dynamics and redox PTM responsiveness to light, defining phage CP12 as a regulatory mimetic that may retune host carbon regulation during infection.
ER  -

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