Structural basis of the conformational changes in Microbacterium hydrocarbonoxydans IclR transcription factor homolog due to ligand binding
Structural basis of the conformational changes in Microbacterium hydrocarbonoxydans IclR transcription factor homolog due to ligand binding
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配体结合引起的氧化碳微杆菌 IclR 转录因子同源物构象变化的结构基础
DOI：
10.1016/j.bbapap.2021.140644
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Yajima Shunsuke
中科院分区：
文献类型：
--
作者：
Akiyama Tomonori;Sasaki Yasuyuki;Ito Shinsaku;Yajima Shunsuke
以非天然酰肼化合物为唯一碳源分离出烃氧化微杆菌。该化合物被细菌酰肼酶水解，并且该酶的基因表达被认为是由异柠檬酸裂解酶调节剂（IclR）家族的转录因子控制的，其属于单组分信号传导系统。最近，我们报道了一个unliganded IclR同系物的晶体结构从mM。烃氧化物，命名为推定的4-羟基苯甲酸反应调节剂（pHbrR），其具有独特的同源四聚体构象。在这项研究中，我们报告的晶体结构的pHbrR络合物与4-羟基苯甲酸，肼酶的催化产物，在2.0 μ m分辨率。pHbrR在未配体状态下形成具有多聚体重排的同源二聚体。凝胶过滤柱层析结果表明二聚体-四聚体重排。我们观察到的环区域覆盖配体结合位点的构象变化，和结构域重排的单体。这项研究报告了第一个配体IclR家族蛋白质结构，该结构证明了配体和非配体蛋白质之间的大规模结构重排，这可能代表了IclR的一般模型。
Microbacteriumhydrocarbonoxydanshas been isolated using an unnatural acylhydrazide compound as the sole carbon source. The compound is hydrolyzed by bacterial hydrazidase, and the gene expression of the enzyme is considered to be controlled by a transcription factor of the Isocitrate lyase Regulator (IclR) family, belonging to the one-component signaling systems. Recently, we reported the crystal structure of an unliganded IclR homolog fromM. hydrocarbonoxydans,named putative 4-hydroxybenzoate response regulator (pHbrR), which has a unique homotetramer conformation. In this study, we report the crystal structure of pHbrR complexed with 4-hydroxybenzoic acid, the catalytic product of hydrazidase, at 2.0 Å resolution. pHbrR forms a homodimer with multimeric rearrangement in the unliganded state. Gel filtration column chromatography results suggested dimer-tetramer rearrangement. We observed conformational change in the loop region covering the ligand-binding site, and domain rearrangements in the monomer. This study reports the first liganded IclR family protein structure that demonstrates large structural rearrangements between liganded and unliganded proteins, which may represent a general model for IclRs.