5tn0
From Proteopedia
Solution Structure of the N-terminal DNA-binding domain of the master biofilm-regulator SinR from Bacillus subtilis
Structural highlights
Function[SINR_BACSU] Negative as well as positive regulator of alternate developmental processes that are induced at the end of vegetative growth in response to nutrient depletion. Binds to the alkaline protease (aprE) gene at two sites. Also acts as a repressor of the key sporulation gene spo0A. Negatively regulates transcription of the eps operon, which is responsible for the biosynthesis of an exopolysaccharide involved in biofilm formation; therefore it could govern the transition between a state in which bacteria swim or swarm and a state in which bacteria assemble into multicellular communities. Acts with Hpr as a corepressor of epr expression. Also negatively regulates transcription of the lutABC operon, which is required for lactate utilization. Repressor activity is regulated by SinI.[1] [2] [3] [4] Publication Abstract from PubMedBacteria have developed numerous protection strategies to ensure survival in harsh environments, with perhaps the most robust method being the formation of a protective biofilm. In biofilms, bacterial cells are embedded within a matrix that is composed of a complex mixture of polysaccharides, proteins and DNA. The Gram-positive bacterium Bacillus subtilis has become a model organism for studying regulatory networks directing biofilm formation. The phenotypic transition from a planktonic to biofilm state is regulated by the activity of the transcriptional repressor, SinR, and its inactivation by its primary antagonist, SinI. In this work, we present the first full-length structural model of tetrameric SinR using a hybrid approach combining high-resolution solution NMR, chemical crosslinking, mass spectrometry, and molecular docking. We also present the solution NMR structure of the antagonist SinI dimer, and probe the mechanism behind the SinR-SinI interaction using a combination of biochemical and biophysical techniques. As a result of these findings, we propose that SinI utilizes a residue replacement mechanism to block SinR multimerization, resulting in diminished DNA binding and concomitant decreased repressor activity. Finally, we provide an evidence-based mechanism that confirms how disruption of the SinR tetramer by SinI regulates gene expression. The Solution Structures and Interaction of SinR and SinI: Elucidating the Mechanism of Action of the Master Regulator Switch for Biofilm Formation in Bacillus subtilis.,Milton ME, Draughn GL, Bobay BG, Stowe SD, Olson AL, Feldmann EA, Thompson RJ, Myers KH, Santoro MT, Kearns DB, Cavanagh J J Mol Biol. 2019 Sep 4. pii: S0022-2836(19)30543-1. doi:, 10.1016/j.jmb.2019.08.019. PMID:31493408[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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