Common Mode of Remodeling AAA ATPases p97/CDC48 by Their Disassembling Cofactors ASPL/PUX1

Abstract

Highlights d Crystal structures of plant ATPase AtCDC48-ND1 and human-plant hybrid complex p97-ND1:PUX1 d PUX1 binds p97-ND1 via a conserved cis-Pro touch-turn motif of its UBX domain d Closed lariat structure in PUX1 involved in binding and disassembly of ATPases d Different thermostability of AtCDC48 and p97 affects the disassembly by PUX1

Versatile control of the CDC48 segregase by the plant UBX-containing (PUX) proteins

“…1 H), thereby competing with p97′s self-association and disrupting the p97 hexamer [23] . The hexamer-disrupting function of this lariat appears preserved in PUX1 [26] , [32] .…”

“…The UBX domain is the general binding domain that enables PUX proteins to associate with CDC48 [35] . UBX is the only PUX domain for which a three-dimensional structure has been determined, namely for A. thaliana PUX1 bound to the human p97 [26] . The PUX1 UBX domain adopts a ubiquitin-like fold.…”

“…PUX1 has been shown to inactivate CDC48A by dissociating the CDC48 hexamer [26] , [32] , [68] . For this, the PUX1 UBX domain binds to the N-terminal of CDC48A, as shown by the hybrid structure of the PUX1 UBX domain in a complex with human p97.…”

“…The capability of PUX1 to dissociate the CDC48 hexamer originates from the N-terminal helical lariat of the PUX1 UBX domain that wraps around the CDC48 monomer ( Fig. 1 H) [26] , [32] , [68] . Lacking additional domains and known functional motifs, the major role of PUX1 appears to be to prevent CDC48A from assembling.…”

“…Ct: C-terminal tail. B: The PUX1 UBX domain (green) in a complex with the N-terminal domain of p97 (p97-N) (white) (PDB 6HD0) [26] . C: Mouse PNGase PUB domain (pink) in complex with the p97 PIM motif (white) (PDB 2HPL) [27] .…”