Structural basis of transcription inhibition by alpha-amanitin and implications 
for RNA polymerase II translocation.

Brueckner, F.; Cramer, P.

doi:10.1038/nsmb.1458

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation.

MPS-Authors

/persons/resource/persons127020

Cramer, P.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

External Resource

http://www.nature.com/nsmb/journal/v15/n8/pdf/nsmb.1458.pdf
(Publisher version)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

1936001.pdf
(Publisher version), 2MB

Supplementary Material (public)

There is no public supplementary material available

Citation

Brueckner, F., & Cramer, P. (2008). Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation. Nature Structural and Molecular Biology, 15, 811-818. doi:10.1038/nsmb.1458.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0015-7C12-B

Abstract

To study how RNA polymerase II translocates after nucleotide incorporation, we prepared elongation complex crystals in which pre- and post-translocation states interconvert. Crystal soaking with the inhibitor alpha-amanitin locked the elongation complex in a new state, which was refined at 3.4-Å resolution and identified as a possible translocation intermediate. The DNA base entering the active site occupies a 'pretemplating' position above the central bridge helix, which is shifted and occludes the templating position. A leucine residue in the trigger loop forms a wedge at the shifted bridge helix, but moves by 13 Å to close the active site during nucleotide incorporation. Our results support a Brownian ratchet mechanism that involves swinging of the trigger loop between open, wedged and closed positions, and suggest that alpha-amanitin impairs nucleotide incorporation and translocation by trapping the trigger loop and bridge helix.