4RBR

Crystal structure of Repressor of Toxin (Rot), a central regulator of Staphylococcus aureus virulence

4RBR の概要

• エントリーDOI: 10.2210/pdb4rbr/pdb
• 分子名称: HTH-type transcriptional regulator rot, CHLORIDE ION (3 entities in total)
• 機能のキーワード: winged-helix-turn-helix, virulence regulator, dna binding, dna binding protein
• 由来する生物種: Staphylococcus aureus subsp. aureus CN1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32964.64

構造登録者

Killikelly, A.,Jakoncic, J.,Sampson, J.M.,Kong, X.-P. (登録日: 2014-09-12, 公開日: 2014-11-05, 最終更新日: 2024-02-28)

主引用文献

Killikelly, A.,Benson, M.A.,Ohneck, E.A.,Sampson, J.M.,Jakoncic, J.,Spurrier, B.,Torres, V.J.,Kong, X.P.
Structure-Based Functional Characterization of Repressor of Toxin (Rot), a Central Regulator of Staphylococcus aureus Virulence.
J.Bacteriol., 197:188-200, 2015

PubMed Abstract: Staphylococcus aureus is responsible for a large number of diverse infections worldwide. In order to support its pathogenic lifestyle, S. aureus has to regulate the expression of virulence factors in a coordinated fashion. One of the central regulators of the S. aureus virulence regulatory networks is the transcription factor repressor of toxin (Rot). Rot plays a key role in regulating S. aureus virulence through activation or repression of promoters that control expression of a large number of critical virulence factors. However, the mechanism by which Rot mediates gene regulation has remained elusive. Here, we have determined the crystal structure of Rot and used this information to probe the contribution made by specific residues to Rot function. Rot was found to form a dimer, with each monomer harboring a winged helix-turn-helix (WHTH) DNA-binding motif. Despite an overall acidic pI, the asymmetric electrostatic charge profile suggests that Rot can orient the WHTH domain to bind DNA. Structure-based site-directed mutagenesis studies demonstrated that R(91), at the tip of the wing, plays an important role in DNA binding, likely through interaction with the minor groove. We also found that Y(66), predicted to bind within the major groove, contributes to Rot interaction with target promoters. Evaluation of Rot binding to different activated and repressed promoters revealed that certain mutations on Rot exhibit promoter-specific effects, suggesting for the first time that Rot differentially interacts with target promoters. This work provides insight into a precise mechanism by which Rot controls virulence factor regulation in S. aureus.

PubMed: 25331435
DOI: 10.1128/JB.02317-14

実験手法

X-RAY DIFFRACTION (1.7 Å)