Ring ATPase assembly and mechanism
A myriad number of essential cellular processes, ranging from DNA replication and chromatin modeling to vesicle trafficking and proteolytic degradation, rely on oligomeric, ring-shaped ATPases for proper function. How a common class of ATPase folds can actively support such a broad number of systems and functions is a wide-ranging basic research question. My group has focused on understanding how certain hexameric members of the RecA and AAA+ ATPase superfamilies act as DNA and RNA motor proteins. We have helped define the structural basis of distinct ring-opening and ring-assembly mechanisms that permit the loading of proteins such as the Rho transcription termination factor and the E1, MCM2-7 and DnaB replicative helicases and onto target nucleic acid subs
trates, and we have helped defined the organization of higher-order helicase assemblies and how accessory factors assist in controlling motor function and mechanism. We also have shown how ATP binding and hydrolysis can be coupled to nucleic acid movement through a hexameric motor, and determined why RecA and AAA+-type hexameric helicases move DNA or RNA with the opposing (5′-3′ vs. 3′-5′) polarities.