Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator
Abstract
MarR (multiple antibiotic resistance repressor) family proteins are bacterial repressors that regulate transcription in response to a wide range of chemical signals. Although specific features of MarR family function have been described, the role of atomic motions in MarRs remains unexplored thus limiting insights into the evolution of allostery in this ubiquitous family of repressors. Here, we provide the first experimental evidence that internal dynamics play a crucial functional role in MarR proteins. Streptococcus pneumoniae AdcR (adhesin-competence repressor) regulates ZnII homeostasis and ZnII functions as an allosteric activator of DNA binding. ZnII coordination triggers a transition from somewhat independent domains to a more compact structure. We identify residues that impact allosteric activation on the basis of ZnII-induced perturbations of atomic motions over a wide range of timescales. These findings appear to reconcile the distinct allosteric mechanisms proposed for other MarRs and highlight the importance of conformational dynamics in biological regulation.
Data availability
NMR datasets were deposited in Biological Magnetic Resonance Bank. Representative data generated or analyzed during this study are included in the supporting files.
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Backbone and side-chain methyl relaxation rates, methyl order parameters, stereospecific resonance assignments, and relaxation rates for Zn(II) AdcRBMRB 27447 (2018-04-09.deposit.bmrb.wisc.edu.80.51213202 for Zn).
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Backbone and side-chain methyl relaxation rates, methyl order parameters, stereospecific resonance assignments, and relaxation rates for apo AdcRBMRB 27448 (2018-04-12.deposit.bmrb.wisc.edu.80.35216533).
Article and author information
Author details
Funding
NIH Office of the Director (GM118157)
- David P Giedroc
Pew Charitable Trusts (Latin American Fellowship)
- Daiana A Capdevila
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Capdevila 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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