Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP.
Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP.
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DOI：
10.1038/nature10215
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发表时间：
2011-07-06
期刊：
影响因子：
64.8
通讯作者：
Hopfner, Karl-Peter
中科院分区：
文献类型：
--
作者：
Wollmann, Petra;Cui, Sheng;Viswanathan, Ramya;Berninghausen, Otto;Wells, Melissa N.;Moldt, Manuela;Witte, Gregor;Butryn, Agata;Wendler, Petra;Beckmann, Roland;Auble, David T.;Hopfner, Karl-Peter
Swi2/Snf2型ATP酶通过催化核小体或其他蛋白质：DNA复合物的破坏、组装或重塑来广泛调节基因组相关过程，例如转录、复制和修复。ATP驱动的运动活动沿着DNA已被建议破坏重塑反应中的靶蛋白：DNA相互作用。然而，复杂和高度特异性的重塑反应知之甚少，主要是因为我们缺乏关于重塑剂如何结合其底物蛋白的高分辨率结构信息。Mot1（转录调节因子1，在人类中表示为BTAF1）是一种Swi2/Snf2酶，其特异性地从启动子DNA中置换TATA盒结合蛋白（TBP），并通过在细胞中产生高度动态的TBP库来全局调节转录。作为一种Swi2/Snf2酶，作为一个单一的多肽和一个相对简单的底物相互作用，Mot1提供了一个理想的系统，更好地了解这个重要的酶家族。为了揭示Mot1如何特异性地破坏TBP：DNA，我们将Mot1：TBP复合物的晶体和电子显微镜结构与生物化学研究相结合。在这里，我们发现Mot1包裹在TBP周围，看起来像一个开瓶器：一个由16个HEAT（亨廷顿蛋白，延伸因子3，PP2A和脂质激酶TOR）重复序列组成的弹簧状阵列通过环插入抓住TBP的DNA远端，而Swi2/Snf2结构域结合上游DNA，定位为通过DNA易位削弱TBP DNA相互作用。一个"闩锁"随后阻断TBP的DNA结合沟，作为一个伴侣，以防止DNA重新联合有效的启动子清除。这项工作显示了重塑酶如何可以联合收割机电机和伴侣的活动，以实现功能特异性使用保守的Swi 2/Snf 2移位酶。
Swi2/Snf2-type ATPases broadly regulate genome-associated processes such as transcription, replication and repair by catalyzing disruption, assembly, or remodeling of nucleosomes or other protein:DNA complexes. ATP-driven motor activity along DNA has been suggested to disrupt target protein:DNA interactions in the remodeling reaction. However, the complex and highly specific remodeling reactions are poorly understood, mostly because we lack high-resolution structural information on how remodelers bind their substrate proteins. Mot1 (modifier of transcription 1, denoted BTAF1 in humans) is a Swi2/Snf2 enzyme that specifically displaces TATA box binding protein (TBP) from promoter DNA and globally regulates transcription by generating a highly dynamic TBP pool in the cell. As a Swi2/Snf2 enzyme that functions as a single polypeptide and interacts with a relatively simple substrate, Mot1 offers an ideal system for a better understanding of this important enzyme family. To reveal how Mot1 specifically disrupts TBP:DNA, we combined crystal and electron microscopy structures of Mot1:TBP complexes with biochemical studies. Here we show that Mot1 wraps around TBP and appears to act like a bottle opener: a spring-like array of 16 HEAT (huntingtin, elongation factor 3, PP2A and lipid kinase TOR) repeats grips the DNA distal side of TBP via loop insertions, while the Swi2/Snf2 domain binds upstream DNA, positioned to weaken TBPs DNA interaction by DNA translocation. A “latch” subsequently blocks TBP’s DNA binding groove, acting as a chaperone to prevent DNA re-association for efficient promoter clearance. This work shows how a remodeling enzyme can combine both motor and chaperone activities to achieve functional specificity using a conserved Swi2/Snf2 translocase.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16
作者：
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通讯作者：
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影响因子：
5.3
作者：
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DOI：
10.1073/pnas.052397899
发表时间：
2002-03-05
影响因子：
11.1
作者：
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通讯作者：
Auble, DT
影响因子：
64.8
作者：
KIM, YC;GEIGER, JH;SIGLER, PB
通讯作者：
SIGLER, PB