Evidence map›Paper›PMID 29550768›Full record

ArticleThe Journal of biological chemistry2018

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

Xiangyang Liu, Lucas Farnung, Christoph Wigge, Patrick Cramer

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Xiangyang LiuDepartment of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Lucas FarnungDepartment of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Christoph WiggeDepartment of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Patrick CramerDepartment of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. Electronic address: pcramer@mpibpc.mpg.de.
Max Planck Institute for Biophysical Chemistry · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 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.

Indexed as

Alpha-AmanitinAmino Acid SequenceAnimalsBinding SitesCryoelectron MicroscopyEnzyme InhibitorsHydrogen BondingProtein ConformationRNA Polymerase IISequence Homology, Amino AcidSwineTranscription Elongation, GeneticAlpha-AmanitinEnzyme InhibitorsRNA Polymerase IIcryo-electron microscopyRNA polymeraseRNA polymerase IIstructural biologytranscription

Identifiers

PMID29550768
PMCPMC5949985
OpenAlexW2791172223

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.