Structure of the Staphylococcus aureus AgrA LytTR Domain Bound to DNA Reveals a Beta Fold with an Unusual Mode of Binding

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Structure

DOI:https://doi.org/10.1016/j.str.2008.02.011· OSTI ID:959993

Sidote, D; Barbieri, C; Wu, T; Stock, A

The LytTR domain is a DNA-binding motif found within the AlgR/AgrA/LytR family of transcription factors that regulate virulence factor and toxin gene expression in pathogenic bacteria. This previously uncharacterized domain lacks sequence similarity with proteins of known structure. The crystal structure of the DNA-binding domain of Staphylococcus aureus AgrA complexed with a DNA pentadecamer duplex has been determined at 1.6 Angstroms resolution. The structure establishes a 10-stranded {beta} fold for the LytTR domain and reveals its mode of interaction with DNA. Residues within loop regions of AgrA contact two successive major grooves and the intervening minor groove on one face of the oligonucleotide duplex, inducing a substantial bend in the DNA. Loss of DNA binding upon substitution of key interacting residues in AgrA supports the observed binding mode. This mode of protein-DNA interaction provides a potential target for future antimicrobial drug design.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959993
• Report Number(s): BNL--82979-2009-JA
• Journal Information: Structure, Journal Name: Structure Journal Issue: 5 Vol. 16
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
BACTERIA
CRYSTAL STRUCTURE
DESIGN
DNA
GENES
OLIGONUCLEOTIDES
PROTEINS
RESIDUES
RESOLUTION
STAPHYLOCOCCUS
TARGETS
TOXINS
TRANSCRIPTION FACTORS
VIRULENCE
national synchrotron light source