Conserved mycobacteriophage protein uses structural mimicry to displace host initiation factors
- 1Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna, Sweden; Science for Life Laboratory, Karolinska Institutet, Solna, Swede
Abstract
Compact viral genomes encode sophisticated strategies to reprogram host gene expression, often by co-opting rather than replacing the host RNA polymerase. How bacteriophages achieve such control in Mycobacteria remains largely unknown. Here, time-resolved interaction proteomics of mycobacteriophage D29 infection identifies a conserved two-protein module, gp53-gp52, that binds the host RNA polymerase. Affinity purification confirmed association of both proteins with the polymerase, while native mass spectrometry demonstrated that gp53 displaces the host sigma factor. Structural modelling places gp53 at the sigma-binding surface of RNA polymerase, consistent with molecular mimicry of sigma-factor engagement. The module is conserved throughout Cluster A mycobacteriophages and occurs in fused or split genomic architectures. These findings suggest sigma-factor displacement as a mechanism of transcriptional takeover in viruses of mycobacteria and show how a compact viral module can repurpose an essential host molecular machine
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BibTeX
@misc{parker2026conserved,
title = {{Conserved mycobacteriophage protein uses structural mimicry to displace host initiation factors}},
author = {D. R. Parker and S. Ghosh and A. Dujiskova and P. D. B. Olinares and S. Narrowe Danielsson and G. I. Prensa and D. Kim and F. A. Rosenberger and A. Elofsson and M. Mann and E. Campbell and A. Fossati},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756390},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756390v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Conserved mycobacteriophage protein uses structural mimicry to displace host initiation factors
AU - D. R. Parker
AU - S. Ghosh
AU - A. Dujiskova
AU - P. D. B. Olinares
AU - S. Narrowe Danielsson
AU - G. I. Prensa
AU - D. Kim
AU - F. A. Rosenberger
AU - A. Elofsson
AU - M. Mann
AU - E. Campbell
AU - A. Fossati
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756390
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756390v1
AB - Compact viral genomes encode sophisticated strategies to reprogram host gene expression, often by co-opting rather than replacing the host RNA polymerase. How bacteriophages achieve such control in Mycobacteria remains largely unknown. Here, time-resolved interaction proteomics of mycobacteriophage D29 infection identifies a conserved two-protein module, gp53-gp52, that binds the host RNA polymerase. Affinity purification confirmed association of both proteins with the polymerase, while native mass spectrometry demonstrated that gp53 displaces the host sigma factor. Structural modelling places gp53 at the sigma-binding surface of RNA polymerase, consistent with molecular mimicry of sigma-factor engagement. The module is conserved throughout Cluster A mycobacteriophages and occurs in fused or split genomic architectures. These findings suggest sigma-factor displacement as a mechanism of transcriptional takeover in viruses of mycobacteria and show how a compact viral module can repurpose an essential host molecular machine
ER -