(A) Proposed mechanism of ESCRT-III translocation by Vps4. W206 and M207 residues of the six Vps4 subunits are shown, with the peptide passing through the Vps4 hexamer. The peptide model was constructed by changing the side chains to leucine without adjusting the main chain, and building out in the N and C directions by overlapping copies of the peptide model. The proposed mechanism envisions that Vps4 progresses through states A to E while bound to successive dipeptides of its substrate. ATP hydrolysis at subunit D destabilizes the DE interface and promotes displacement of subunit E toward the transitioning subunit F configuration, which allows displacement of ADP. Subsequent ATP binding allows subunit F to pack against subunit A, bind to the next dipeptide of ESCRT-III, and assume the subunit A configuration. (BC) Conservation of helical pore loop structure in AAA ATPases. Overlap on the large ATPases of multiple AAA ATPase structures gives a similar helical arrangement of pore loop 1 residues from five subunits. (B) Top and (C) side views are shown of the ESCRT-III peptide (green) and Vps4 pore loop 1 (red) with the equivalent residues of: VAT (Ripstein et al., 2017) (pdbid 5vca), HSP104 (Gates et al., 2017) (5vjh), NSF (Zhao et al., 2015) (3j94), human 26S proteasome (Huang et al., 2016) (5gjr), yeast 26S proteasome (Wehmer et al., 2017) (5mp9), katanin (Zehr et al., 2017) (5wc0, 5wcb).