p97 belongs to the superfamily of AAA+ ATPases and is characterized by a tandem
AAA module, an N-terminal domain involved in substrate and cofactor
interactions, and a functionally important unstructured C-terminal tail. The
ATPase activity is controlled by an intradomain communication within the same
protomer and an interdomain communication between neighboring protomers. Here,
we present for the first time crystal structures in which the physiologically
relevant p97 hexamer constitutes the content of the asymmetric unit, namely in
the apo state without nucleotide in either the D1 or D2 module and in the
pre-activated state with ATPĪ³S bound to both modules. The structures provide
new mechanistic insights into the interdomain communication mediated by
conformational changes of the C terminus as well as an intersubunit signaling
network, which couples the nucleotide state to the conformation of the central
putative substrate binding pore.
