Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P.

Published

Journal Article

Carbon catabolite repression (CCR) is one of the most fundamental environmental-sensing mechanisms in bacteria and imparts competitive advantage by establishing priorities in carbon metabolism. In gram-positive bacteria, the master transcription regulator of CCR is CcpA. CcpA is a LacI-GalR family member that employs, as an allosteric corepressor, the phosphoprotein HPr-Ser46-P, which is formed in glucose-replete conditions. Here we report structures of the Bacillus megaterium apoCcpA and a CcpA-(HPr-Ser46-P)-DNA complex. These structures reveal that HPr-Ser46-P mediates a novel two-component allosteric DNA binding activation mechanism that involves both rotation of the CcpA subdomains and relocation of pivot-point residue Thr61, which leads to juxtaposition of the DNA binding regions permitting "hinge" helix formation in the presence of cognate DNA. The structure of the CcpA-(HPr-Ser46-P)-cre complex also reveals the elegant mechanism by which CcpA family-specific interactions with HPr-Ser46-P residues Ser46-P and His15 partition the high-energy CCR and low-energy PTS pathways, the latter requiring HPr-His15-P.

Full Text

Duke Authors

Cited Authors

  • Schumacher, MA; Allen, GS; Diel, M; Seidel, G; Hillen, W; Brennan, RG

Published Date

  • September 17, 2004

Published In

Volume / Issue

  • 118 / 6

Start / End Page

  • 731 - 741

PubMed ID

  • 15369672

Pubmed Central ID

  • 15369672

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2004.08.027

Language

  • eng

Conference Location

  • United States