Press Releases
Dec. 2, 2010

A novel mechanism to inhibit bacterial gene expression

— A spiky transcription factor sticks and stops RNA polymerase —
Presenters
  • Shigeyuki Yokoyama (Laboratory of Structural Biology, Graduate School of Science, University of Tokyo. RIKEN Systems and Structural Biology Center)
  • Shun-ichi Sekine (Laboratory of Structural Biology, Graduate School of Science, University of Tokyo. RIKEN Systems and Structural Biology Center)
  • Shunsuke Tagami (RIKEN Systems and Structural Biology Center)

Abstract

Figure 1

Figure 1. A schematic showing transcription of DNA into RNA by RNA polymerase.

NTP is the substrate for RNA synthesis. RNA polymerase incorporates NTPs via its entry channel, and synthesizes RNA by adding them one by one to the RNA end.

Figure 2

Figure 2. Structure of RNA polymerase complexed with Gfh1

Figure 3

Figure 3. Mechanism of RNA polymerase inhibition by Gfh1

For the cellar gene expression, RNA is first synthesized by copying the sequence of a part of DNA (transcription), and then a protein is synthesized based on the RNA sequence (translation). This process is known as the central dogma of molecular biology, and is essential for all biological processes. RNA polymerase is the enzyme responsible for the transcription. Here, we report the crystal structure of a bacterial RNA polymerase complexed with a protein transcription factor (Gfh1) that inhibits the RNA polymerase. The structure reveals a unique mechanism by which Gfh1 inhibits the RNA polymerase. Gfh1 inserts its protruded part into the RNA polymerase substrate (NTP) entry channel, and fully occludes the substrate entry. Moreover, the RNA polymerase assumes a previously unidentified conformation with an enlarged nucleic-acid binding channel, and the Gfh1 was found to force this conformation to inhibit the polymerase. The newly found mechanism of the transcription inhibition will be the basis for future development of brand-new antibiotics.

Paper information

Shunsuke Tagami, Shun-ichi Sekine, Thirumananseri Kumarevel, Nobumasa Hino, Yuko Murayama, Shunsuke Kamegamori, Masaki Yamamoto, Kensaku Sakamoto & Shigeyuki Yokoyama, Crystal structure of bacterial RNA polymerase bound with a transcription inhibitor protein, Nature, Published online 01 December 2010.