6exv

Publication Abstract from PubMed

RNA polymerase II (Pol II) is the central enzyme that transcribes eukaryotic protein-coding genes to produce mRNA. The mushroom toxin alpha-amanitin binds Pol II and inhibits transcription at the step of RNA chain elongation. Pol II from yeast binds alpha-amanitin with micromolar affinity, whereas metazoan Pol II enzymes exhibit nanomolar affinities. Here, we present the high-resolution cryo-EM structure of alpha-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 alpha-amanitin and highlights that cryo-EM is well suited to studying interactions of a small molecule with its macromolecular target.

Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by alpha-amanitin.,Liu X, Farnung L, Wigge C, Cramer P J Biol Chem. 2018 Mar 17. pii: RA118.002545. doi: 10.1074/jbc.RA118.002545. PMID:29550768^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.