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Mechanism of DNA translocation underlying chromatin remodelling by Snf2

机译：Snf2重塑染色质的DNA易位机制

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摘要

Chromatin remodellers include diverse enzymes with distinct biological functions, but nucleosome-sliding activity appears to be a common theme(1,2). Among the remodelling enzymes, Snf2 serves as the prototype to study the action of this protein family. Snf2 and related enzymes share two conserved RecA-like lobes(3), which by themselves are able to couple ATP hydrolysis to chromatin remodelling. The mechanism by which these enzymes couple ATP hydrolysis to translocate the nucleosome along the DNA remains unclear(2,4-8). Here we report the structures of Saccharomyces cerevisiae Snf2 bound to the nucleosome in the presence of ADP and ADP-BeFx. Snf2 in the ADP-bound state adopts an open conformation similar to that in the apo state, and induces a one-base-pair DNA bulge at superhelix location 2 (SHL2), with the tracking strand showing greater distortion than the guide strand. The DNA distortion propagates to the proximal end, leading to staggered translocation of the two strands. The binding of ADP-BeFx triggers a closed conformation of the enzyme, resetting the nucleosome to a relaxed state. Snf2 shows altered interactions with the DNA in different nucleotide states, providing the structural basis for DNA translocation. Together, our findings suggest a fundamental mechanism for the DNA translocation that underlies chromatin remodelling.
机译：染色质重塑剂包括具有不同生物学功能的多种酶，但核小体滑动活性似乎是一个共同的主题（1,2）。在重塑酶中，Snf2作为研究该蛋白家族作用的原型。 Snf2和相关的酶共有两个保守的RecA样叶（3），它们本身能够将ATP水解与染色质重塑耦合。这些酶与ATP水解以沿着DNA转移核小体的机制尚不清楚（2,4-8）。在这里，我们报告啤酒酵母Snf2绑定到ADP和ADP-BeFx存在的核小体的结构。处于ADP结合状态的Snf2采用类似于apo态的开放构象，并在超螺旋位置2（SHL2）处诱导一个碱基对的DNA凸起，跟踪链显示出比引导链更大的畸变。 DNA变形传播到近端，导致两条链的错位。 ADP-BeFx的结合触发了酶的封闭构象，将核小体重置为松弛状态。 Snf2在不同的核苷酸状态下显示出与DNA相互作用的改变，为DNA移位提供了结构基础。在一起，我们的发现提出了染色质重塑基础的DNA易位的基本机制。

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  • 来源
    《Nature》 |2019年第7748期|409-413|共5页
  • 作者

    Li Meijing; Xia Xian; Tian Yuanyuan; Jia Qi; Liu Xiaoyu; Lu Ying; Li Ming; Li Xueming; Chen Zhucheng;

  • 作者单位

    Tsinghua Univ, MOE Key Lab Prot Sci, Beijing, Peoples R China|Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China|Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China|Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China;

    Tsinghua Univ, MOE Key Lab Prot Sci, Beijing, Peoples R China|Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China|Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China;

    Tsinghua Univ, MOE Key Lab Prot Sci, Beijing, Peoples R China|Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China|Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China|Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China;

    Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Inst Phys, Beijing, Peoples R China|Chinese Acad Sci, CAS Key Lab Soft Matter Phys, Inst Phys, Beijing, Peoples R China;

    Tsinghua Univ, MOE Key Lab Prot Sci, Beijing, Peoples R China|Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China|Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China|Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China;

    Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Inst Phys, Beijing, Peoples R China|Chinese Acad Sci, CAS Key Lab Soft Matter Phys, Inst Phys, Beijing, Peoples R China;

    Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Inst Phys, Beijing, Peoples R China|Chinese Acad Sci, CAS Key Lab Soft Matter Phys, Inst Phys, Beijing, Peoples R China;

    Tsinghua Univ, MOE Key Lab Prot Sci, Beijing, Peoples R China|Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China|Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China|Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China;

    Tsinghua Univ, MOE Key Lab Prot Sci, Beijing, Peoples R China|Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China|Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China|Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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