The Structure and Mechanism of the ATPase that Powers Viral Genome Packaging

Abstract

Many viruses actively package their genomes into preformed procapsids using a dedicated ATPase machine that is among the most powerful known biological motors. However, the structural mechanism by which this packaging motor couples ATP hydrolysis to DNA translocation is still unknown. Here we describe crystal structures of the packaging motor ATPase domain that exhibit nucleotide‐dependent conformational changes involving a 13° rotation of an entire subdomain. We also identify the arginine finger residue that catalyzes ATP hydrolysis in the ATPase domain of a neighboring motor subunit. The ATPase domain structures and identification of the arginine finger allow us to derive a structural model for the motor ring. We validate this model with a combination of small angle x‐ray scattering, ATPase measurements, DNA‐binding assays, and comparison with a previous cryo‐ electron microscopy reconstruction. Finally, we integrate our results to propose a mechanistic model for DNA translocation by this molecular machine.