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Structural basis of transcription inhibition by the DNA mimic protein Ocr of bacteriophage T7

Ye, Fuzhou; Kotta-Loizou, Ioly; Jovanovic, Milija; Liu, Xiaojiao; Dryden, David TF; Buck, Martin; Zhang, Xiaodong

Structural basis of transcription inhibition by the DNA mimic protein Ocr of bacteriophage T7 Thumbnail


Authors

Fuzhou Ye

Ioly Kotta-Loizou

Milija Jovanovic

Xiaojiao Liu

Martin Buck

Xiaodong Zhang



Abstract

Bacteriophage T7 infects Escherichia coli and evades the host restriction/modification system. The Ocr protein of T7 was shown to exist as a dimer mimicking DNA and to bind to host restriction enzymes, thus preventing the degradation of the viral genome by the host. Here we report that Ocr can also inhibit host transcription by directly binding to bacterial RNA polymerase (RNAP) and competing with the recruitment of RNAP by sigma factors. Using cryo electron microscopy, we determined the structures of Ocr bound to RNAP. The structures show that an Ocr dimer binds to RNAP in the cleft, where key regions of sigma bind and where DNA resides during transcription synthesis, thus providing a structural basis for the transcription inhibition. Our results reveal the versatility of Ocr in interfering with host systems and suggest possible strategies that could be exploited in adopting DNA mimicry as a basis for forming novel antibiotics.

Citation

Ye, F., Kotta-Loizou, I., Jovanovic, M., Liu, X., Dryden, D. T., Buck, M., & Zhang, X. (2020). Structural basis of transcription inhibition by the DNA mimic protein Ocr of bacteriophage T7. eLife, 9, Article e52125. https://doi.org/10.7554/elife.52125

Journal Article Type Article
Acceptance Date Feb 8, 2020
Online Publication Date Feb 10, 2020
Publication Date 2020
Deposit Date Apr 1, 2020
Publicly Available Date Mar 28, 2024
Journal eLife
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 9
Article Number e52125
DOI https://doi.org/10.7554/elife.52125

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
© Copyright Ye et al. This article is distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use and redistribution provided that the
original author and source are credited.




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