5YDW

Full-length structure of HypT from Salmonella typhimuriuma (hypochlorite-specific LysR-type transcriptional regulator)

5YDW の概要

• エントリーDOI: 10.2210/pdb5ydw/pdb
• 分子名称: Cell density-dependent motility repressor (1 entity in total)
• 機能のキーワード: hocl, hocl-specific transcription factor, lysr-type transcription regulator, hypochlorous acid, hypochlorite, dna binding protein
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69397.00

構造登録者

Jo, I.,Hong, S.,Ahn, J.,Ha, N.C. (登録日: 2017-09-15, 公開日: 2018-11-28, 最終更新日: 2023-11-22)

主引用文献

Jo, I.,Kim, D.,No, T.,Hong, S.,Ahn, J.,Ryu, S.,Ha, N.C.
Structural basis for HOCl recognition and regulation mechanisms of HypT, a hypochlorite-specific transcriptional regulator.
Proc. Natl. Acad. Sci. U.S.A., 116:3740-3745, 2019

PubMed Abstract: Hypochlorous acid (HOCl) is generated in the immune system to kill microorganisms. In , a hypochlorite-specific transcription regulator, HypT, has been characterized. HypT belongs to the LysR-type transcriptional regulator (LTTR) family that contains a DNA-binding domain (DBD) and a regulatory domain (RD). Here, we identified a gene from serovar Typhimurium and determined crystal structures of the full-length HypT protein and the RD. The full-length structure reveals a type of tetrameric assembly in the LTTR family. Based on HOCl-bound and oxidation-mimicking structures, we identified a HOCl-driven methionine oxidation mechanism, in which the bound HOCl oxidizes a conserved methionine residue lining the putative ligand-binding site in the RD. Furthermore, we proposed a molecular model for the oxidized HypT, where methionine oxidation by HOCl results in a conformational change of the RD, inducing a counter rotation of the DBD dimers. Target genes that are regulated by HypT and their roles in were also investigated. DNase I footprinting experiments revealed a DNA segment containing two pseudopalindromic motifs that are separated by ∼100 bp, suggesting that only the oxidized structure makes a concomitant binding, forming a DNA loop. An understanding of the HypT-mediated mechanism would be helpful for controlling many pathogenic bacteria by counteracting bacterial HOCl defense mechanisms.

PubMed: 30733296
DOI: 10.1073/pnas.1811509116

実験手法

X-RAY DIFFRACTION (3.3 Å)