How a DNA polymerase clamp loader opens a sliding clamp

Science. 2011 Dec 23;334(6063):1675-80. doi: 10.1126/science.1211884.

Abstract

Processive chromosomal replication relies on sliding DNA clamps, which are loaded onto DNA by pentameric clamp loader complexes belonging to the AAA+ family of adenosine triphosphatases (ATPases). We present structures for the ATP-bound state of the clamp loader complex from bacteriophage T4, bound to an open clamp and primer-template DNA. The clamp loader traps a spiral conformation of the open clamp so that both the loader and the clamp match the helical symmetry of DNA. One structure reveals that ATP has been hydrolyzed in one subunit and suggests that clamp closure and ejection of the loader involves disruption of the ATP-dependent match in symmetry. The structures explain how synergy among the loader, the clamp, and DNA can trigger ATP hydrolysis and release of the closed clamp on DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Bacteriophage T4
  • Binding Sites
  • Crystallography, X-Ray
  • DNA, A-Form / chemistry*
  • DNA, A-Form / metabolism
  • DNA, Viral / chemistry*
  • DNA, Viral / metabolism
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / metabolism*
  • Hydrolysis
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Static Electricity
  • Templates, Genetic
  • Trans-Activators / chemistry*
  • Trans-Activators / metabolism
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism

Substances

  • DNA, A-Form
  • DNA, Viral
  • Protein Subunits
  • Trans-Activators
  • Viral Proteins
  • gene 44 protein, Enterobacteria phage T4
  • gene 45 protein, Enterobacteria phage T4
  • gp62 protein, bacteriophage T4
  • Adenosine Triphosphate
  • DNA-Directed DNA Polymerase
  • Adenosine Triphosphatases

Associated data

  • PDB/3U5Z
  • PDB/3U60
  • PDB/3U61