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Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors
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SYSNO ASEP 0525126 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors Author(s) Pandey, Saurabh Kumar (MBU-M) ORCID
Melicherčík, Milan (MBU-M)
Řeha, David (MBU-M) ORCID
Ettrich, Rüdiger (MBU-M)
Carey, Jannette (MBU-M) ORCIDArticle number 2247 Source Title Molecules. - : MDPI
Roč. 25, č. 9 (2020)Number of pages 24 s. Language eng - English Country CH - Switzerland Keywords entropy ; global motion ; salt bridges Subject RIV BO - Biophysics OECD category Biophysics R&D Projects GA13-21053S GA ČR - Czech Science Foundation (CSF) LM2015055 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure CESNET II - 90042 - CESNET - zájmové sdružení právnických osob Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 000535695900243 EID SCOPUS 85084466508 DOI 10.3390/molecules25092247 Annotation Hexameric arginine repressor, ArgR, is the feedback regulator of bacterial L-arginine regulons, and sensor of L-arg that controls transcription of genes for its synthesis and catabolism. Although ArgR function, as well as its secondary, tertiary, and quaternary structures, is essentially the same in E. coli and B. subtilis, the two proteins differ significantly in sequence, including residues implicated in the response to L-arg. Molecular dynamics simulations are used here to evaluate the behavior of intact B. subtilis ArgR with and without L-arg, and are compared with prior MD results for a domain fragment of E. coli ArgR. Relative to its crystal structure, B. subtilis ArgR in absence of L-arg undergoes a large-scale rotational shift of its trimeric subassemblies that is very similar to that observed in the E. coli protein, but the residues driving rotation have distinct secondary and tertiary structural locations, and a key residue that drives rotation in E. coli is missing in B. subtilis. The similarity of trimer rotation despite different driving residues suggests that a rotational shift between trimers is integral to ArgR function. This conclusion is supported by phylogenetic analysis of distant ArgR homologs reported here that indicates at least three major groups characterized by distinct sequence motifs but predicted to undergo a common rotational transition. The dynamic consequences of L-arg binding for transcriptional activation of intact ArgR are evaluated here for the first time in two-microsecond simulations of B. subtilis ArgR. L-arg binding to intact B. subtilis ArgR causes a significant further shift in the angle of rotation between trimers that causes the N-terminal DNA-binding domains lose their interactions with the C-terminal domains, and is likely the first step toward adopting DNA-binding-competent conformations. The results aid interpretation of crystal structures of ArgR and ArgR-DNA complexes. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2021 Electronic address https://www.mdpi.com/1420-3049/25/9/2247
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