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.

journal_name

Elife

journal_title

eLife

authors

Capdevila DA,Huerta F,Edmonds KA,Le MT,Wu H,Giedroc DP

doi

10.7554/eLife.37268

subject

Has Abstract

pub_date

2018-10-17 00:00:00

issn

2050-084X

pii

37268

journal_volume

7

pub_type

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