Out-of-plane motions in open sliding clamps: Molecular dynamics simulations of eukaryotic and archaeal proliferating cell nuclear antigen

Steven L. Kazmirski, Yanxiang Zhao, Gregory D. Bowman, Mike O'Donnell, John Kuriyan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

53 Citations (Scopus)


Sliding clamps are ring-like multimeric proteins that encircle duplex DNA and serve as mobile DNA-bound platforms that are essential for efficient DNA replication and repair. Sliding clamps are placed on DNA by clamp loader complexes, in which the clamp-interacting elements are organized in a right-handed spiral assembly. To understand how the flat, ring-like clamps might interact with the spiral interaction surface of the clamp loader complex, we have performed molecular dynamics simulations of sliding clamps (proliferating cell nuclear antigen from the budding yeast, humans, and an archaeal species) in which we have removed one of the three subunits so as to release the constraint of ring closure. The simulations reveal significant structural fluctuations corresponding to lateral opening and out-of-plane distortions of the clamp, which result principally from bending and twisting of the β-sheets that span the intermolecular interfaces, with smaller but similar contributions from -sheets that span the intramolecular interfaces within each subunit. With the integrity of these β-sheets intact, the predominant fluctuations seen in the simulations are oscillations between lateral openings and right-handed spirals. The tendency for clamps to adopt a right-handed spiral conformation implies that once opened, the conformation of the clamp can easily match the spiraling of clamp loader subunits, a feature that is intrinsic to the recognition of DNA and subsequent hydrolysis of ATP by the clamp-bound clamp loader complex.
Original languageEnglish
Pages (from-to)13801-13806
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
Publication statusPublished - 27 Sep 2005
Externally publishedYes


  • β-sheet distortion
  • Clamp loader
  • Conformational transitions
  • DNA replication
  • DNA sliding clamps

ASJC Scopus subject areas

  • General


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