Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA
- The Rockefeller University, United States
- Sloan-Kettering Institute, United States
- University of Cambridge, United States
Abstract
RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish thatRbpA and CarD cooperatively stimulate formation of anintermediate (RP2) leading to RPo; formation of RP2 islikely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2.We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcriptionby RbpA and CarD.
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Article and author information
Author details
Michael S Glickman
Funding
National Institutes of Health (RO1 GM114450)
- Elizabeth A Campbell
National Institutes of Health (P30 CA008748)
- Michael S Glickman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- James M Berger, Johns Hopkins University School of Medicine, United States
Version history
- Received: October 19, 2016
- Accepted: January 7, 2017
- Accepted Manuscript published: January 9, 2017 (version 1)
- Version of Record published: February 10, 2017 (version 2)
Copyright
© 2017, Hubin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA
eLife 6:e22520.
https://doi.org/10.7554/eLife.22520
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