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Title: 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.

Authors:
ORCiD logo [1];  [2];  [1];  [1];  [1]; ORCiD logo [3]
  1. Department of Chemistry, Indiana University, Bloomington, United States
  2. Department of Chemistry, Indiana University, Bloomington, United States; Graduate Program in Biochemistry, Indiana University, Bloomington, United States
  3. Department of Chemistry, Indiana University, Bloomington, United States; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHOTHER
OSTI Identifier:
1502254
Resource Type:
Journal Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 7; Journal Issue: 10, 2018; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Capdevila, Daiana A., Huerta, Fidel, Edmonds, Katherine A., Le, My Tra, Wu, Hongwei, and Giedroc, David P.. Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator. United States: N. p., 2018. Web. doi:10.7554/eLife.37268.
Capdevila, Daiana A., Huerta, Fidel, Edmonds, Katherine A., Le, My Tra, Wu, Hongwei, & Giedroc, David P.. Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator. United States. doi:10.7554/eLife.37268.
Capdevila, Daiana A., Huerta, Fidel, Edmonds, Katherine A., Le, My Tra, Wu, Hongwei, and Giedroc, David P.. Wed . "Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator". United States. doi:10.7554/eLife.37268.
@article{osti_1502254,
title = {Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator},
author = {Capdevila, Daiana A. and Huerta, Fidel and Edmonds, Katherine A. and Le, My Tra and Wu, Hongwei and Giedroc, David P.},
abstractNote = {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.},
doi = {10.7554/eLife.37268},
journal = {eLife},
issn = {2050-084X},
number = 10, 2018,
volume = 7,
place = {United States},
year = {2018},
month = {10}
}