The Magic Spot: a PpGpp Binding Site on E. Coli RNA Polymerase Responsible for Regulation of Transcription Initiation

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Apr 30

PMID 23623682

Citations 170

Authors

Wilma Ross

Catherine E Vrentas

Patricia Sanchez-Vazquez

Tamas Gaal

Richard L Gourse

Affiliations

Soon will be listed here.

Abstract

The global regulatory nucleotide ppGpp ("magic spot") regulates transcription from a large subset of Escherichia coli promoters, illustrating how small molecules can control gene expression promoter-specifically by interacting with RNA polymerase (RNAP) without binding to DNA. However, ppGpp's target site on RNAP, and therefore its mechanism of action, has remained unclear. We report here a binding site for ppGpp on E. coli RNAP, identified by crosslinking, protease mapping, and analysis of mutant RNAPs that fail to respond to ppGpp. A strain with a mutant ppGpp binding site displays properties characteristic of cells defective for ppGpp synthesis. The binding site is at an interface of two RNAP subunits, ω and β', and its position suggests an allosteric mechanism of action involving restriction of motion between two mobile RNAP modules. Identification of the binding site allows prediction of bacterial species in which ppGpp exerts its effects by targeting RNAP.

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