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-Structure paper
| タイトル | Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by α-amanitin. |
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| ジャーナル・号・ページ | J Biol Chem, Vol. 293, Issue 19, Page 7189-7194, Year 2018 |
| 掲載日 | 2018年5月11日 |
著者 | Xiangyang Liu / Lucas Farnung / Christoph Wigge / Patrick Cramer / ![]() |
| PubMed 要旨 | RNA polymerase II (Pol II) is the central enzyme that transcribes eukaryotic protein-coding genes to produce mRNA. The mushroom toxin α-amanitin binds Pol II and inhibits transcription at the step ...RNA polymerase II (Pol II) is the central enzyme that transcribes eukaryotic protein-coding genes to produce mRNA. The mushroom toxin α-amanitin binds Pol II and inhibits transcription at the step of RNA chain elongation. Pol II from yeast binds α-amanitin with micromolar affinity, whereas metazoan Pol II enzymes exhibit nanomolar affinities. Here, we present the high-resolution cryo-EM structure of α-amanitin bound to and inhibited by its natural target, the mammalian Pol II elongation complex. The structure revealed that the toxin is located in a pocket previously identified in yeast Pol II but forms additional contacts with metazoan-specific residues, which explains why its affinity to mammalian Pol II is ∼3000 times higher than for yeast Pol II. Our work provides the structural basis for the inhibition of mammalian Pol II by the natural toxin α-amanitin and highlights that cryo-EM is well suited to studying interactions of a small molecule with its macromolecular target. |
リンク | J Biol Chem / PubMed:29550768 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.6 Å |
| 構造データ | |
| 化合物 | ![]() ChemComp-ZN: ![]() ChemComp-MG: |
| 由来 |
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キーワード | TRANSCRIPTION / Inhibitor / elongation / active site |
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amanita phalloides (タマゴテングタケ)
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