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  Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by α-amanitin.

Liu, X., Farnung, L., Wigge, C., & Cramer, P. (2018). Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by α-amanitin. Journal of Biological Chemistry, 293(19), 7189-7194. doi:10.1074/jbc.RA118.002545.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-F47E-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-8654-7
Genre: Journal Article

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Liu, X.1, Author              
Farnung, L.1, Author              
Wigge, C.1, Author              
Cramer, P.1, Author              
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1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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 Abstract: 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 explain 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.

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Language(s): eng - English
 Dates: 2018-03-172018-05-11
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1074/jbc.RA118.002545
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Title: Journal of Biological Chemistry
Source Genre: Journal
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Pages: - Volume / Issue: 293 (19) Sequence Number: - Start / End Page: 7189 - 7194 Identifier: -