ATP‐dependent control of auto‐assembly and DNA remodeling by the AAA+ replication initiation factor, DnaA

P‐loop NTPases comprise as many as 10–20% of the proteins in a cell and are widespread throughout all domains of life. A subset form higher‐order oligomeric structures and transduce chemical energy derived from ATP into conformational changes that can perform work. The bacterial replication initiation factor DnaA falls within the AAA+ subfamily of NTPases, a broad grouping of evolutionarily related enzymes that variously move and remodel target macromolecules for numerous cellular transactions. When bound to ATP, monomeric DnaA localizes to replication origins and subsequently forms a large nucleoprotein complex that unwinds DNA and directs replisome assembly. Using structural analyses, we show how ATP binding induces conformational changes in DnaA that permit the initiator to self‐associate into a right‐handed helical assembly. DNA topology studies show that this quaternary arrangement actively wraps origin DNA into a supercoil about the DnaA oligomer. Together, these findings provide a molecular framework for understanding how DnaA transitions between monomer and multimer states, and how modifications of the AAA+ fold permit DnaA to reorganize chromosome superstructure and control multiple aspects of DNA replication initiation in an ATP‐dependent manner.