The transition to an elongation complex by T7 RNA polymerase is a multistep process

J Biol Chem. 2007 Aug 3;282(31):22879-86. doi: 10.1074/jbc.M702589200. Epub 2007 Jun 4.

Abstract

During the transition from an initiation complex to an elongation complex (EC), T7 RNA polymerase undergoes major conformational changes that involve reorientation of a "core" subdomain as a rigid body and extensive refolding of other elements in the 266 residue N-terminal domain. The pathway and timing of these events is poorly understood. To examine this, we introduced proline residues into regions of the N-terminal domain that become alpha-helical during the reorganization and changed the charge of a key residue that interacts with the RNA:DNA hybrid 5 bp upstream of the active site in the EC but not in the initiation complex. These alterations resulted in a diminished ability to make products >5-7 nt and/or a slow transition through this point. The results indicate that the transition to an EC is a multistep process and that the movement of the core subdomain and reorganization of certain elements in the N-terminal domain commence prior to promoter release (at 8-9 nt).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacteriophage T7 / metabolism
  • Base Sequence
  • Binding Sites
  • DNA / chemistry
  • DNA-Directed RNA Polymerases / chemistry*
  • Kinetics
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA / chemistry
  • Trypsin / chemistry
  • Viral Proteins / chemistry*

Substances

  • Viral Proteins
  • RNA
  • DNA
  • bacteriophage T7 RNA polymerase
  • DNA-Directed RNA Polymerases
  • Trypsin