title: Crystal structure of DNA polymerase III β sliding clamp from Mycobacterium tuberculosis.
abstract: The sliding clamp is a key component of DNA polymerase III (Pol III) required for genome replication. It is known to function with diverse DNA repair proteins and cell cycle-control proteins, making it a potential drug target. To extend our understanding of the structure/function relationship of the sliding clamp, we solved the crystal structure of the sliding clamp from Mycobacterium tuberculosis (M. tuberculosis), a human pathogen that causes most cases of tuberculosis (TB). The sliding clamp from M. tuberculosis forms a ring-shaped head-to-tail dimer with three domains per subunit. Each domain contains two α helices in the inner ring that lie against two β sheets in the outer ring. Previous studies have indicated that many Escherichia coli clamp-binding proteins have a conserved LF sequence, which is critical for binding to the hydrophobic region of the sliding clamp. Here, we analyzed the binding affinities of the M. tuberculosis sliding clamp and peptides derived from the α and δ subunits of Pol III, which indicated that the LF motif also plays an important role in the binding of the α and δ subunits to the sliding clamp of M. tuberculosis.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Gui
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Lin
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhang
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Bi
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004258:DNA Polymerase III / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; C101139:beta subunit, DNA polymerase III; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; C083980:dnaN protein, Bacteria