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6exv

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Structure of mammalian RNA polymerase II elongation complex inhibited by Alpha-amanitin

6exv, resolution 3.60Å

Structural highlights

6exv is a 16 chain structure with sequence from Amanita phalloides, Sus scrofa and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	DNA-directed RNA polymerase, with EC number 2.7.7.6
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RPB9_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template (By similarity). [I3LGP4_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU363031] [I3LCB2_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively.[PIRNR:PIRNR000779] [I3LJR4_PIG] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU004279] [AAMAT_AMAPH] Major toxin belonging to the bicyclic octapeptides amatoxins that acts by binding non-competitively to RNA polymerase II and greatly slowing the elongation of transcripts from target promoters (PubMed:4865716, PubMed:363352, PubMed:7642577, PubMed:8702941).^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

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

References

↑ Wieland T, Faulstich H. Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms. CRC Crit Rev Biochem. 1978 Dec;5(3):185-260. PMID:363352
↑ Wieland T. Poisonous principles of mushrooms of the genus Amanita. Four-carbon amines acting on the central nervous system and cell-destroying cyclic peptides are produced. Science. 1968 Mar 1;159(3818):946-52. PMID:4865716
↑ Chafin DR, Guo H, Price DH. Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA polymerase II. J Biol Chem. 1995 Aug 11;270(32):19114-9. PMID:7642577
↑ Rudd MD, Luse DS. Amanitin greatly reduces the rate of transcription by RNA polymerase II ternary complexes but fails to inhibit some transcript cleavage modes. J Biol Chem. 1996 Aug 30;271(35):21549-58. PMID:8702941
↑ Li P, Deng W, Li T. The molecular diversity of toxin gene families in lethal Amanita mushrooms. Toxicon. 2014 Jun;83:59-68. doi: 10.1016/j.toxicon.2014.02.020. Epub 2014 Mar 5. PMID:24613547 doi:http://dx.doi.org/10.1016/j.toxicon.2014.02.020
↑ Liu X, Farnung L, Wigge C, Cramer P. Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by alpha-amanitin. J Biol Chem. 2018 Mar 17. pii: RA118.002545. doi: 10.1074/jbc.RA118.002545. PMID:29550768 doi:http://dx.doi.org/10.1074/jbc.RA118.002545

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6exv"

@@ Line 3: / Line 3: @@
 <SX load='6exv' size='340' side='right' viewer='molstar' caption='[[6exv]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6exv]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Amanita_phalloides Amanita phalloides], [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EXV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EXV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6exv]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Amanita_phalloides Amanita phalloides], [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EXV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6EXV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=ILX:4,5-DIHYDROXYISOLEUCINE'>ILX</scene>, <scene name='pdbligand=TRX:6-HYDROXYTRYPTOPHAN'>TRX</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6exv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6exv OCA], [http://pdbe.org/6exv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6exv RCSB], [http://www.ebi.ac.uk/pdbsum/6exv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6exv ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6exv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6exv OCA], [http://pdbe.org/6exv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6exv RCSB], [http://www.ebi.ac.uk/pdbsum/6exv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6exv ProSAT]</span></td></tr>
 </table>
 == Function ==

6exv

From Proteopedia

Current revision

Structure of mammalian RNA polymerase II elongation complex inhibited by Alpha-amanitin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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