Crystal Structure of the Transcriptional Regulator CmeR From Campylobacter Jejuni

Journal Article · Mon Jun 01 04:00:00 EDT 2009 · J. Mol. Biol 372:583,2007

OSTI ID:953987

Gu, R; Su, C -C; Shi, F; McDermott, G; Zhang, Q; Yu, E W

The CmeABC multidrug efflux pump, which belongs to the resistance-nodulation-division (RND) family, recognizes and extrudes a broad range of antimicrobial agents and is essential for Campylobacter jejuni colonization of the animal intestinal tract by mediating the efflux of bile acids. The expression of CmeABC is controlled by the transcriptional regulator CmeR, whose open reading frame is located immediately upstream of the cmeABC operon. To understand the structural basis of CmeR regulation, we have determined the crystal structure of CmeR to 2.2 {angstrom} resolution, revealing a dimeric two-domain molecule with an entirely helical architecture similar to members of the TetR family of transcriptional regulators. Unlike the rest of the TetR regulators, CmeR has a large center-to-center distance (54 {angstrom}) between two N termini of the dimer, and a large flexible ligand-binding pocket in the C-terminal domain. Each monomer forms a 20 {angstrom} long tunnel-like cavity in the ligand-binding domain of CmeR and is occupied by a fortuitous ligand that is identified as glycerol. The binding of glycerol to CmeR induces a conformational state that is incompatible with target DNA. As glycerol has a chemical structure similar to that of potential ligands of CmeR, the structure obtained mimics the induced form of CmeR. These findings reveal novel structural features of a TetR family regulator, and provide new insight into the mechanisms of ligand binding and CmeR regulation.

• Research Organization: Stanford Linear Accelerator Center (SLAC)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 953987
• Report Number(s): SLAC-REPRINT-2009-405
• Journal Information: J. Mol. Biol 372:583,2007, Journal Name: J. Mol. Biol 372:583,2007 Vol. 372; ISSN JMOBAK; ISSN 0022-2836
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ANIMALS
ANTIMICROBIAL AGENTS
BACTERIA
BILE ACIDS
CRYSTAL STRUCTURE
DNA
GLYCEROL
LIGANDS
MOLECULES
MONOMERS
Other
OTHER
BIO
TRANSCRIPTION