Crystal structures of the transcriptional repressor RolR reveals a novel recognition mechanism between inducer and regulator.
Crystal structures of the transcriptional repressor RolR reveals a novel recognition mechanism between inducer and regulator.
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DOI：
10.1371/journal.pone.0019529
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发表时间：
2011-05-03
期刊：
影响因子：
3.7
通讯作者：
Wang DC
中科院分区：
文献类型：
--
作者：
Li DF;Zhang N;Hou YJ;Huang Y;Hu Y;Zhang Y;Liu SJ;Wang DC
TetR家族的许多成员控制着与多药耐药和致病相关的基因的转录。RolR(R Esorcin Ol R Egator)是最近从谷氨酸棒杆菌中发现的一种芳香族分解代谢的TetR型调节剂，其特点是序列相似性低，调控不同于已知的TetR家族成员。在这里，我们报道了RolR在其效应器结合形式(与间苯二酚结合)和AOP形式中的晶体结构，分别为2.5？和3.6？间苯二酚-RolR络合物的结构表明，四个基序(Asp94-Arg145-Arg148-Asp149)与两个水分子之间的氢键网络和五个残基(Phe107、Leu111、Leu114、Leu142和Phe172)的疏水相互作用是间苯二酚与RolR分子识别和结合的关键因素。当效应器结合时，识别螺旋h3-h3‘的中心到中心的间隔从34.9？减少到30.4？这种结构变化导致RolR不适合与DNA结合。这些观察结果与TetR其他成员的观察结果不同。对RolR进行了基于结构的突变，结果证实了上述残基对效应器结合的特异性和亲和力的关键作用。相似的序列搜索和序列比对从GenBank中鉴定出29个RolR同源物，所有上述残基在同源物中都高度保守。基于这些结构和其他功能的研究，我们认为RolR可能代表了一个新的TetR蛋白亚家族，它们参与了芳香族的降解，并与RolR具有共同的识别模式。
Many members of the TetR family control the transcription of genes involved in multidrug resistance and pathogenicity. RolR (R esorcin ol R egulator), the recently reported TetR-type regulator for aromatic catabolism from Corynebacterium glutamicum, distinguishes itself by low sequence similarities and different regulation from the previously known members of the TetR family. Here we report the crystal structures of RolR in its effector-bound (with resorcinol) and aop- forms at 2.5 Å and 3.6 Å, respectively. The structure of resorcinol-RolR complex reveal that the hydrogen-bonded network mediated by the four-residue motif (Asp94- Arg145- Arg148- Asp149) with two water molecules and the hydrophobic interaction via five residues (Phe107, Leu111, Leu114, Leu142, and Phe172) are the key factors for the recognition and binding between the resorcinol and RolR molecules. The center-to-center separation of the recognition helices h3-h3′ is decreased upon effector-binding from 34.9 Å to 30.4 Å. This structural change results in that RolR was unsuitable for DNA binding. Those observations are distinct from that in other TetR members. Structure-based mutagenesis on RolR was carried out and the results confirmed the critical roles of the above mentioned residues for effector-binding specificity and affinity. Similar sequence searches and sequence alignments identified 29 RolR homologues from GenBank, and all the above mentioned residues are highly conserved in the homologues. Based on these structural and other functional investigations, it is proposed that RolR may represent a new subfamily of TetR proteins that are invovled in aromatic degradation and sharing common recognition mode as for RolR.
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影响因子：
5.6
作者：
Natsume, R;Ohnishi, Y;Horinouchi, S
通讯作者：
Horinouchi, S
影响因子：
3.2
作者：
BECK, CF;MUTZEL, R;MULLER, W
通讯作者：
MULLER, W
DOI：
10.1107/s0907444906035712
发表时间：
2006-11-01
影响因子：
2.2
作者：
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通讯作者：
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DOI：
10.1038/8263
发表时间：
1999-05-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
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作者：
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通讯作者：
Lamzin, VS
影响因子：
4.8
作者：
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通讯作者：
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