Structural basis for the recognition of sulfur in phosphorothioated DNA.

Structural basis for the recognition of sulfur in phosphorothioated DNA.
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硫代磷酸化 DNA 中硫的识别的结构基础

DOI:
10.1038/s41467-018-07093-1
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发表时间:
2018-11-08
影响因子:
16.6
通讯作者:
He X
He X
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu G;Fu W;Zhang Z;He Y;Yu H;Wang Y;Wang X;Zhao YL;Deng Z;Wu G;He X

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关于特异性识别硫的蛋白质结构域的报道很少。在这里,我们提出的硫结合结构域(SBD)的DNA硫代磷酸化(PT)依赖性限制性内切酶ScoMcrA的晶体结构。SBD含有疏水表面腔,其由Y164的芳环、P165的吡咯烷环和用作腔的盖、底和壁的四个其他残基的非极性侧链形成。SBD和PT-DNA在结合时经历构象变化。S187 RGRR 191环插入DNA大沟中,与GPSGCC核心序列的碱基接触。突变SBD的关键残基损害PT-DNA缔合。来自14个门的1000多个测序的微生物物种含有SBD同源物。我们发现,这些同系物结合PT-DNA在体外和限制PT-DNA基因转移在体内。这些结果表明,SBD类PT-DNA阅读器广泛存在于原核生物中。DNA硫代磷酸化(PT-DNA)是一种DNA骨架硫修饰,可被IV型限制性内切酶ScoMcrA识别。在这里,作者通过解决来自ScoMcrA的PT-DNA结合硫结合结构域(SBD)的晶体结构来提供对硫识别的见解,并且他们进一步表明SBD同系物在原核生物中广泛分布。
There have been very few reports on protein domains that specifically recognize sulfur. Here we present the crystal structure of the sulfur-binding domain (SBD) from the DNA phosphorothioation (PT)-dependent restriction endonuclease ScoMcrA. SBD contains a hydrophobic surface cavity that is formed by the aromatic ring of Y164, the pyrolidine ring of P165, and the non-polar side chains of four other residues that serve as lid, base, and wall of the cavity. The SBD and PT-DNA undergo conformational changes upon binding. The S187RGRR191 loop inserts into the DNA major groove to make contacts with the bases of the GPSGCC core sequence. Mutating key residues of SBD impairs PT-DNA association. More than 1000 sequenced microbial species from fourteen phyla contain SBD homologs. We show that three of these homologs bind PT-DNA in vitro and restrict PT-DNA gene transfer in vivo. These results show that SBD-like PT-DNA readers exist widely in prokaryotes. DNA phosphorothioation (PT-DNA) is a DNA backbone sulfur modification that is recognized by the type-IV restriction endonuclease ScoMcrA. Here the authors provide insights into sulfur recognition by solving the crystal structure of the PT-DNA bound sulfur-binding domain (SBD) from ScoMcrA and they further show that SBD homologs are widely spread among prokaryotes.
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