Structural Basis of Transcription Activation: The CAP-αCTD-DNA Complex

Benoff, Brian
Yang, Huanwang
Lawson, Catherine L.
Parkinson, Gary
Liu, Jinsong
Blatter, Erich
Ebright, Yon W.
Berman, Helen M.
Ebright, Richard H.

¹Waksman Institute and Department of Chemistry, ²Howard Hughes Medical Institute, Rutgers University, Piscataway, NJ 08854, USA.

*Present address: CRC Biomolecular Structure Unit, Institute of Cancer Research, London SW3 6JB, UK.

†Present address: Tularik Inc., South San Francisco, CA 94080, USA.

‡Present address: Human Genome Sciences Inc., Rockville, MD 20874, USA.

§To whom correspondence on crystallographic issues should be addressed. E-mail: [email protected]

∥To whom correspondence on all other issues should be addressed. E-mail: [email protected]

Supporting Online Material: www.sciencemag.org/cgi/content/full/297/5586/1562/DC1; Figs. S1 and S2

19 July 2002; accepted 29 July 2002

Science 297(5586):p 1562-1566, August 30, 2002.

The Escherichia coli catabolite activator protein (CAP) activates transcription at P_lac, P_gal, and other promoters through interactions with the RNA polymerase α subunit carboxyl-terminal domain (αCTD). We determined the crystal structure of the CAP-αCTD-DNA complex at a resolution of 3.1 angstroms. CAP makes direct protein-protein interactions with αCTD, and αCTD makes direct protein-DNA interactions with the DNA segment adjacent to the DNA site for CAP. There are no large-scale conformational changes in CAP and αCTD, and the interface between CAP and αCTD is small. These findings are consistent with the proposal that activation involves a simple "recruitment" mechanism.