Testing mechanisms of DNA sliding by architectural DNA-binding proteins: dynamics of single wild-type and mutant protein molecules in vitro and in vivo.
Testing mechanisms of DNA sliding by architectural DNA-binding proteins: dynamics of single wild-type and mutant protein molecules in vitro and in vivo.
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DOI：
10.1093/nar/gkab658
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发表时间：
2021-09-07
影响因子：
14.9
通讯作者：
Johnson RC
中科院分区：
文献类型：
--
作者：
Kamagata K;Itoh Y;Tan C;Mano E;Wu Y;Mandali S;Takada S;Johnson RC
建筑DNA结合蛋白（Architectural DNA binding proteins，ADBPs）是真核生物或细菌染色体中的重要组成部分，能与DNA结合并参与多种DNA反应。它们在结合时在DNA中产生大的构象变化，但在寻找功能结合位点时可以沿DNA沿着。在这里，我们调查的机制，ADBP扩散的DNA突变蛋白质的单分子分析，合理选择区分旋转耦合扩散和DNA表面滑动后，短暂的解结合的凹槽（S）。酵母Nhp 6A突变蛋白的性质，结合分子动力学模拟，表明Nhp 6A在两种结合模式之间切换：一种是静止状态，其中HMGB结构域结合在小沟内，DNA高度弯曲，另一种是移动的状态，其中蛋白质通过其柔性N-末端碱性臂沿着DNA表面移动。Fis突变体的行为，细菌的类核苷酸相关的螺旋-转角-螺旋二聚体，最好用从大沟解结合并沿着DNA表面扩散的移动的蛋白质来解释。Nhp 6A、Fis和细菌HU都几乎完全与染色体相关，如包装在细菌类核内，并且可以通过三种扩散模式来建模，其中HU表现出最快的扩散，Fis表现出最慢的扩散。
Architectural DNA-binding proteins (ADBPs) are abundant constituents of eukaryotic or bacterial chromosomes that bind DNA promiscuously and function in diverse DNA reactions. They generate large conformational changes in DNA upon binding yet can slide along DNA when searching for functional binding sites. Here we investigate the mechanism by which ADBPs diffuse on DNA by single-molecule analyses of mutant proteins rationally chosen to distinguish between rotation-coupled diffusion and DNA surface sliding after transient unbinding from the groove(s). The properties of yeast Nhp6A mutant proteins, combined with molecular dynamics simulations, suggest Nhp6A switches between two binding modes: a static state, in which the HMGB domain is bound within the minor groove with the DNA highly bent, and a mobile state, where the protein is traveling along the DNA surface by means of its flexible N-terminal basic arm. The behaviors of Fis mutants, a bacterial nucleoid-associated helix-turn-helix dimer, are best explained by mobile proteins unbinding from the major groove and diffusing along the DNA surface. Nhp6A, Fis, and bacterial HU are all near exclusively associated with the chromosome, as packaged within the bacterial nucleoid, and can be modeled by three diffusion modes where HU exhibits the fastest and Fis the slowest diffusion.
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影响因子：
11.4
作者：
Allain, FHT;Yen, YM;Feigon, J
通讯作者：
Feigon, J
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
3.2
作者：
BALL, CA;OSUNA, R;JOHNSON, RC
通讯作者：
JOHNSON, RC
DOI：
10.1016/s0378-4371(02)01038-5
发表时间：
2002-10-01
影响因子：
3.3
作者：
Bruinsma, RF
通讯作者：
Bruinsma, RF
影响因子：
16.6
作者：
Cuculis, Luke;Abil, Zhanar;Zhao, Huimin;Schroeder, Charles M.
通讯作者：
Schroeder, Charles M.