Structure of an OhrR-ohrA operator complex reveals the DNA binding mechanism of the MarR family
Structure of an OhrR-ohrA operator complex reveals the DNA binding mechanism of the MarR family
复制标题
DOI：
10.1016/j.molcel.2005.09.013
复制
发表时间：
2005-10-07
期刊：
影响因子：
16
通讯作者：
Brennan, RG
中科院分区：
文献类型：
--
作者：
Hong, M;Fuangthong, M;Brennan, RG
作为转录调控因子MarR家族的一员，枯草芽孢杆菌OhrR结合ohrA操作符，并被有机氢过氧化物氧化成硫酸诱导，其机制尚不清楚。本文描述了还原OhrR和OhrR- ohra算子配合物的晶体结构。为了结合DNA， OhrR采用了一个嵌合翼的螺旋-旋转-螺旋DNA结合基序，该基序由延伸的真核样翅膀、原核螺旋-旋转-螺旋基序和螺旋-螺旋元件组成。过氧化物感应半胱氨酸的反应活性不受近端碱性残基的调节，而主要受螺旋α 1的正偶极子的调节。诱导源于氧化传感器半胱氨酸的硫酸部分与附近的酪氨酸和蛋氨酸之间的亚基间位冲突的缓解。OhrR-ohrA操作复合体的结构揭示了整个MarR家族的DNA结合机制，并提示存在一个共同的诱导剂结合袋。
The mechanisms by which Bacillus subtilis OhrR, a member of the MarR family of transcription regulators, binds the ohrA operator and is induced by oxidation of its lone cysteine residue by organic hydroperoxides to sulphenic acid are unknown. Here, we describe the crystal structures of reduced OhrR and an OhrR-ohrA operator complex. To bind DNA, OhrR employs a chimeric winged helix-turn-helix DNA binding motif, which is composed of extended eukaryotic-like wings, prokaryotic helix-turn-helix motifs, and helix-helix elements. The reactivity of the peroxidesensing cysteine is not modulated by proximal basic residues but largely by the positive dipole of helix alpha 1. Induction originates from the alleviation of intersubunit steric clash between the sulphenic acid moieties of the oxidized sensor cysteines and nearby tyrosines and methionines. The structure of the OhrR-ohrA operator complex reveals the DNA binding mechanism of the entire MarR family and suggests a common inducer binding pocket.