RNAP Laboratory, Institute for Structural and Molecular Biology, University College London, London, UK.
Institute for Structural and Molecular Biology, Birkbeck College, London, UK.
Nat Commun. 2021 Sep 17;12(1):5523. doi: 10.1038/s41467-021-25666-5.
RNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural bases underlying RNAP inhibition in archaea. The Acidianus two-tailed virus encodes the RIP factor that binds inside the DNA-binding channel of RNAP, inhibiting transcription by occlusion of binding sites for nucleic acid and the transcription initiation factor TFB. Infection with the Sulfolobus Turreted Icosahedral Virus induces the expression of the host factor TFS4, which binds in the RNAP funnel similarly to eukaryotic transcript cleavage factors. However, TFS4 allosterically induces a widening of the DNA-binding channel which disrupts trigger loop and bridge helix motifs. Importantly, the conformational changes induced by TFS4 are closely related to inactivated states of RNAP in other domains of life indicating a deep evolutionary conservation of allosteric RNAP inhibition.
RNA 聚合酶抑制在响应环境变化和病毒-宿主关系中的转录调控中起着重要作用。在这里，我们呈现了两个这样的 RNAP-抑制剂复合物的高分辨率结构，为古菌中的 RNAP 抑制提供了结构基础。Acidianus 双尾病毒编码的 RIP 因子结合在 RNAP 的 DNA 结合通道内，通过阻塞核酸结合位点和转录起始因子 TFB 来抑制转录。感染 Sulfolobus Turreted Icosahedral 病毒会诱导宿主因子 TFS4 的表达，它类似于真核转录切割因子一样结合在 RNAP 的漏斗中。然而，TFS4 别构诱导 DNA 结合通道变宽，破坏触发环和桥螺旋模体。重要的是，TFS4 诱导的构象变化与其他生命领域中 RNAP 的失活状态密切相关，表明别构 RNAP 抑制具有深刻的进化保守性。
