Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6 transcription factor Pho7 and its role in phosphate homeostasis.
Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6 transcription factor Pho7 and its role in phosphate homeostasis.
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DOI：
10.1093/nar/gky827
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发表时间：
2018-11-30
影响因子：
14.9
通讯作者：
Shuman S
中科院分区：
文献类型：
--
作者：
Garg A;Goldgur Y;Schwer B;Shuman S
Pho 7是真菌转录因子Zn 2Cys 6家族的一员，是裂殖酵母磷酸盐稳态的关键转录激活因子，磷酸盐稳态是对磷酸盐饥饿的生理反应，其中pho 1，pho 84和tgp 1基因被上调。在这里，我们描绘了一个最小化的61个氨基酸的Pho 7 DNA结合域（DBD），并确定了1.7 μ m的晶体结构的DBD在其目标位点的tgp 1启动子。Pho 7 DBD的两个显著特征是：它结合DNA作为单体，不像大多数其他真菌锌簇因子结合作为同源二聚体;它与其不对称靶序列在14 bp足迹上进行广泛的相互作用，这需要氢键结合到CGG三联体内的13个单独的碱基，并且远离CGG三联体，CGG三联体通常由其他Zn 2Cys 6 DBD识别。tgp 1和pho 1启动子中Pho 7位点的碱基对取代突出了5′-CGG三联体对于Pho 7体外结合和Pho 7依赖性基因体内表达的重要性。我们确定了几个DBD氨基酸丙氨酸取代消除或减弱的pho 1磷酸饥饿反应和一致减少pho 7结合到pho 1启动子位点。
Pho7, a member of the Zn2Cys6 family of fungal transcription factors, is the key transcriptional activator underlying fission yeast phosphate homeostasis, a physiological response to phosphate starvation in which the pho1, pho84 and tgp1 genes are upregulated. Here, we delineated a minimized 61-amino-acid Pho7 DNA-binding domain (DBD) and determined the 1.7 Å crystal structure of the DBD at its target site in the tgp1 promoter. Two distinctive features of the Pho7 DBD are: it binds DNA as a monomer, unlike most other fungal zinc-cluster factors that bind as homodimers; and it makes extensive interactions with its asymmetric target sequence over a 14-bp footprint that entails hydrogen bonding to 13 individual bases within, and remote from, the CGG triplet typically recognized by other Zn2Cys6 DBDs. Base pair substitutions at Pho7 sites in the tgp1 and pho1 promoters highlight the importance of the 5′-CGG triplet for Pho7 binding in vitro and Pho7-dependent gene expression in vivo. We identify several DBD amino acids at which alanine substitution effaced or attenuated the pho1 phosphate starvation response and concordantly reduced Pho7 binding to a pho1 promoter site.
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DOI：
10.1107/s2059798317016035
发表时间：
2018-02-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Potterton L;Agirre J;Ballard C;Cowtan K;Dodson E;Evans PR;Jenkins HT;Keegan R;Krissinel E;Stevenson K;Lebedev A;McNicholas SJ;Nicholls RA;Noble M;Pannu NS;Roth C;Sheldrick G;Skubak P;Turkenburg J;Uski V;von Delft F;Waterman D;Wilson K;Winn M;Wojdyr M
通讯作者：
Wojdyr M
影响因子：
14.9
作者：
Blanchet C;Pasi M;Zakrzewska K;Lavery R
通讯作者：
Lavery R
DOI：
10.1261/rna.056515.116
发表时间：
2016-07
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Chatterjee D;Sanchez AM;Goldgur Y;Shuman S;Schwer B
通讯作者：
Schwer B
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
影响因子：
5.7
作者：
Cahuzac, B;Cerdan, R;Guittet, E
通讯作者：
Guittet, E