Self-organization of parS centromeres by the ParB CTP hydrolase
Self-organization of parS centromeres by the ParB CTP hydrolase
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DOI：
10.1126/science.aay3965
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发表时间：
2019-11-29
期刊：
影响因子：
56.9
通讯作者：
Gruber, Stephan
中科院分区：
文献类型：
--
作者：
Soh, Young-Min;Davidson, Iain Finley;Gruber, Stephan
ParABS系统促进细菌和古细菌中的染色体分离和质粒分配。ParB蛋白结合着丝粒parS DNA序列并扩散到侧翼DNA。我们表明，ParB是一种酶，水解胞苷三磷酸（CTP）的胞苷二磷酸（CDP）。parS DNA通过ParB和CTP水解刺激协同CTP结合。核苷酸共晶结构阐明了二聚化依赖性的ParB CTtlase的催化中心。单分子成像和生化分析概括了在CTP存在但不存在的情况下ParB从parS扩散的特征。这些发现表明，着丝粒组装的自加载的ParB DNA滑动夹在parS。ParB CTR4与已知的核苷酸水解酶无关，可能是开发新类别抗生素的有希望的靶点。
ParABS systems facilitate chromosome segregation and plasmid partitioning in bacteria and archaea. ParB protein binds centromeric parS DNA sequences and spreads to flanking DNA. We show that ParB is an enzyme that hydrolyzes cytidine triphosphate (CTP) to cytidine diphosphate (CDP). parS DNA stimulates cooperative CTP binding by ParB and CTP hydrolysis. A nucleotide cocrystal structure elucidates the catalytic center of the dimerization-dependent ParB CTPase. Single-molecule imaging and biochemical assays recapitulate features of ParB spreading from parS in the presence but not absence of CTP. These findings suggest that centromeres assemble by self-loading of ParB DNA sliding clamps at parS. ParB CTPase is not related to known nucleotide hydrolases and might be a promising target for developing new classes of antibiotics.