Stringent control of the RNA-dependent RNA polymerase translocation revealed by multiple intermediate structures
Stringent control of the RNA-dependent RNA polymerase translocation revealed by multiple intermediate structures
复制标题
多个中间结构揭示了RNA依赖性RNA聚合酶易位的严格控制
DOI：
10.1038/s41467-020-16234-4
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发表时间：
2020-05-25
影响因子：
16.6
通讯作者：
Gong, Peng
中科院分区：
文献类型：
--
作者：
Wang, Meihua;Li, Rui;Gong, Peng
Each polymerase nucleotide addition cycle is associated with two primary conformational changes of the catalytic complex: the pre-chemistry active site closure and post-chemistry translocation. While active site closure is well interpreted by numerous crystallographic snapshots, translocation intermediates are rarely captured. Here we report three types of intermediate structures in an RNA-dependent RNA polymerase (RdRP). The first two types, captured in forward and reverse translocation events, both highlight the role of RdRP-unique motif G in restricting the RNA template movement, corresponding to the rate-limiting step in translocation. By mutating two critical residues in motif G, we obtain the third type of intermediates that may mimic the transition state of this rate-limiting step, demonstrating a previously unidentified movement of the template strand. We propose that a similar strategy may be utilized by other classes of nucleic acid polymerases to ensure templating nucleotide positioning for efficient catalysis through restricting interactions with template RNA.
