Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors.
Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors.
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DOI：
10.1093/nar/gkt009
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发表时间：
2013-04-01
影响因子：
14.9
通讯作者：
Sello JK
中科院分区：
文献类型：
--
作者：
Davis JR;Brown BL;Page R;Sello JK
马尔R家族蛋白是一组由超过12000个转录调控因子组成的基因组，它们在细菌和古细菌基因组中编码，控制代谢、应激反应、毒力和多药耐药性中的基因表达。有很多兴趣在定义的分子机制，配体结合减弱这些蛋白质的DNA结合活性。在这里，我们描述了PcaV，天蓝色链霉菌中的马尔R家族调节因子，如何通过其与途径底物原儿茶酸的相互作用来控制编码β-酮己二酸途径酶的基因的转录。该转录抑制因子是已知的唯一调节芳香族catenin的这一重要途径的马尔R蛋白。在体外试验中，原儿茶酸和其他酚类化合物破坏PcaV-DNA复合物。我们发现，PcaV结合原儿茶酸在1：1的化学计量与任何马尔家族成员的最高亲和力。此外，我们报告的结构PcaV在其载脂蛋白的形式和复杂的原儿茶酸。我们确定了一个精氨酸残基，这是配体协调的关键，并证明它也需要结合DNA。我们建议，配体与精氨酸残基的相互作用决定了调节DNA结合的构象变化。我们的研究结果提供了新的见解的分子机制，配体衰减DNA结合在这个大家族的转录因子。
MarR family proteins constitute a group of >12 000 transcriptional regulators encoded in bacterial and archaeal genomes that control gene expression in metabolism, stress responses, virulence and multi-drug resistance. There is much interest in defining the molecular mechanism by which ligand binding attenuates the DNA-binding activities of these proteins. Here, we describe how PcaV, a MarR family regulator in Streptomyces coelicolor, controls transcription of genes encoding β-ketoadipate pathway enzymes through its interaction with the pathway substrate, protocatechuate. This transcriptional repressor is the only MarR protein known to regulate this essential pathway for aromatic catabolism. In in vitro assays, protocatechuate and other phenolic compounds disrupt the PcaV–DNA complex. We show that PcaV binds protocatechuate in a 1:1 stoichiometry with the highest affinity of any MarR family member. Moreover, we report structures of PcaV in its apo form and in complex with protocatechuate. We identify an arginine residue that is critical for ligand coordination and demonstrate that it is also required for binding DNA. We propose that interaction of ligand with this arginine residue dictates conformational changes that modulate DNA binding. Our results provide new insights into the molecular mechanism by which ligands attenuate DNA binding in this large family of transcription factors.
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影响因子：
16
作者：
Hong, M;Fuangthong, M;Brennan, RG
通讯作者：
Brennan, RG
影响因子：
8
作者：
Andresen, Cecilia;Jalal, Shah;Sunnerhagen, Maria
通讯作者：
Sunnerhagen, Maria
影响因子：
3.2
作者：
Chubiz, Lon M.;Rao, Christopher V.
通讯作者：
Rao, Christopher V.
影响因子：
4.8
作者：
Hong, HJ;Hutchings, MI;Buttner, MJ
通讯作者：
Buttner, MJ
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH