VCP and UFD1L:NPLOC4 bind the ubiquitinated nascent peptide and extract it from the 60S ribosomal subunit (inferred from yeast homologs in Defenouillère et al. 2013, Verma et al. 2013, reviewed in Meyer and van den Boom 2023). The UFD1L:NPLOC4 heterodimer (UFD1:NPL4 in yeast) acts as an adapter that binds K48-linked polyubiquitin, unfolds one ubiquitin moiety, and inserts it into the pore of the VCP hexamer to initiate degradation of the substrate protein (inferred from yeast homologs in Williams et al. 2023, reviewed in Meyer and van den Boom 2023).
Six subunits of VCP surround the substrate protein, which is located in the central pore of the hexamer. Hydrolysis of ATP by a VCP subunit causes it to disengage from the hexamer. Release of ADP and binding of ATP causes the subunit to rebind the hexamer more proximally to the 60S ribosomal subunit (reviewed in Meyer and van den Boom 2023). The result is a ratcheting effect that withdraws the nascent peptide from the 60S subunit. The extracted nascent peptide remains bound to the ribosome-associated quality control complex (RQC complex, LTN1:NEMF:TCF25:VCP hexamer) which dissociates from the 60S ribosomal subunit and escorts the nascent peptide to the proteasome (inferred from yeast homologs in Defenouillère et al. 2017).