A bridge to transcription by RNA polymerase

Craig D Kaplan,Roger D Kornberg

doi:10.1186/jbiol99

Abstract

A comprehensive survey of single amino-acid substitution mutations critical for RNA polymerase function published in Journal of Biology supports a proposed mechanism for polymerase action in which movement of the polymerase 'bridge helix' promotes transcriptional activity in cooperation with a critical substrate-interaction domain, the 'trigger loop'.

Highlights

Initial structural studies on the prokaryotic and eukaryotic enzymes identified a conserved alpha-helical domain, termed the bridge helix, that spans between two main lobes of the enzyme
The bridge helix appeared in two separate conformations - ‘straight’ in a eukaryotic RNA polymerases (RNAPs) structure and ‘kinked’ in a bacterial RNAP structure - raising the possibility that the conformational dynamics of the bridge might directly control enzyme translocation: that is, bending of the bridge helix might accompany movement of the polymerase along the DNA template
A second limitation of crystal structures is that they only provide snapshots of stable conformations, failing to fully reveal the dynamics involved in catalysis of phosphodiester bond formation and translocation of RNAP along the template

Summary

Introduction

Initial structural studies on the prokaryotic and eukaryotic enzymes identified a conserved alpha-helical domain, termed the bridge helix, that spans between two main lobes of the enzyme (for a useful bibliography of the structural literature on RNA polymerase, see Tan et al [1]). X-ray crystallographic studies on multisubunit RNA polymerases (RNAPs) from eukaryotes, bacteria and archaea have revealed highly related enzymes with structurally conserved active sites. For eukaryotic and bacterial enzymes, crystal structures of transcribing complexes have been solved, showing the locations of the DNA template, the nascent RNA product and the substrate-binding site.

Results

Conclusion