Conformational analysis of processivity clamps demonstrates that tertiary structure does not correlate with dynamics
Lead Presenter: Philip Nevin
Additional Presenters: Jing Fang John R. Engen Penny J. Beuning
Faculty Advisor/Principal Investigator: Dr. Penny J. Beuning
Method of Presentation: Poster
All living organisms share the ability to replicate DNA so that the information necessary for life can be inherited. This process requires the coordination of multiple enzymes and regulatory proteins, including DNA polymerases and processivity clamps. The processivity clamps are ring-shaped oligomers that are structurally and functionally conserved throughout evolution. These clamps are essential cofactors in DNA replication since they encircle DNA and tether the DNA polymerase to the DNA template thereby enabling processive replication. In addition, the processivity clamp serves as a moving hub for various protein-protein interactions, including those involving DNA repair proteins and specialized DNA polymerases that carry out replication of damaged DNA. Although the three-dimensional structure of various sliding clamps are highly similar, they share very little sequence homology. In this research we have used hydrogen exchange mass spectrometry (HXMS) to probe the conformational dynamics of processivity clamps from bacteriophage, bacteria, archaea, and eukaryotes. Our data reveals that the highly conserved tertiary structure does not correlate with the conformational dynamics of the proteins. Interestingly, the processivity clamps found in bacteria seem to be more dynamic than those found in archaea and eukaryotes.