Structural basis for substrate loading in bacterial RNA polymerase

Dmitry G. Vassylyev (), Marina N. Vassylyeva, Jinwei Zhang, Murali Palangat, Irina Artsimovitch and Robert Landick
Additional contact information
Dmitry G. Vassylyev: University of Alabama at Birmingham, Schools of Medicine and Dentistry, 402B Kaul Genetics Building, 720 20th Street South, Birmingham, Alabama 35294, USA
Marina N. Vassylyeva: University of Alabama at Birmingham, Schools of Medicine and Dentistry, 402B Kaul Genetics Building, 720 20th Street South, Birmingham, Alabama 35294, USA
Jinwei Zhang: Department of Biomolecular Chemistry,
Murali Palangat: Department of Biochemistry and,
Irina Artsimovitch: The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA
Robert Landick: Department of Biochemistry and,

Nature, 2007, vol. 448, issue 7150, 163-168

Abstract: Abstract The mechanism of substrate loading in multisubunit RNA polymerase is crucial for understanding the general principles of transcription yet remains hotly debated. Here we report the 3.0-Å resolution structures of the Thermus thermophilus elongation complex (EC) with a non-hydrolysable substrate analogue, adenosine-5′-[(α,β)-methyleno]-triphosphate (AMPcPP), and with AMPcPP plus the inhibitor streptolydigin. In the EC/AMPcPP structure, the substrate binds to the active (‘insertion’) site closed through refolding of the trigger loop (TL) into two α-helices. In contrast, the EC/AMPcPP/streptolydigin structure reveals an inactive (‘preinsertion’) substrate configuration stabilized by streptolydigin-induced displacement of the TL. Our structural and biochemical data suggest that refolding of the TL is vital for catalysis and have three main implications. First, despite differences in the details, the two-step preinsertion/insertion mechanism of substrate loading may be universal for all RNA polymerases. Second, freezing of the preinsertion state is an attractive target for the design of novel antibiotics. Last, the TL emerges as a prominent target whose refolding can be modulated by regulatory factors.

Date: 2007
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/nature05931 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:448:y:2007:i:7150:d:10.1038_nature05931

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05931

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().