Conserved mycobacteriophage protein uses structural mimicry to displace host initiation factors

Authors

Parker, D. R., Ghosh, S., Dujiskova, A., Olinares, P. D. B., Narrowe Danielsson, S., Prensa, G. I., Kim, D., Rosenberger, F. A., Elofsson, A., Mann, M., Campbell, E., Fossati, A.

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

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 06 Oct 2026.

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