Structural basis of ubiquitin-independent PP1 complex disassembly by p97

Abstract

The AAA+ ATPase p97 (also called VCP, or Cdc48 in yeast) unfolds proteins and disassembles protein complexes in a myriad of cellular processes, but how a substrate complex needs to be loaded onto p97 by a dedicated substrate adapter and then disassembled by p97 has not been structurally visualized so far. Here we present cryo-EM structures of p97 in the process of disassembling a protein phosphatase-1 (PP1) complex by stripping off an inhibitory subunit. We show that PP1 and its partners SDS22 and inhibitor-3 (I3) bind to a peripheral N-domain of p97 via a direct contact between SDS22 and a groove in the N-domain. A density consistent with the SHP box of the p37 adapter binds to the same N-domain underneath the PP1 complex, while the p37-UBX domain is found on the adjacent N-domain. I3 is likely represented by three densities.