The VPS131-335 fragment is located at the wider end of the VPS131-1390 “basket.” (A) VPS131-335 coordinates (Protein Data Bank accession no. 6CBC) were docked into the part of the EM map colored yellow in Fig. 1, A and B (top) and fitted (bottom). (B) VPS13 may function as a channel for lipid transfer between membranes. Intact VPS13 resembles a bubble wand (De et al., 2017); the portion corresponding to VPS131-1390 is blue. Mutations were introduced to render the N-terminal or middle portion of the channel hydrophilic, as indicated here and in Fig. 1 B. VPS13 may cooperate with protein partners to ensure directional lipid transport. (C) Changes in mut1 are indicated here in a model of S. cerevisiae VPS13 based on the crystal structure of Vps131-335 (Protein Data Bank accession no. 6CBC): L64K/I80E/L87E/I162R/L185E/A192E/L217R/V269E/L275D/M293K/L300R. Mutations in mut2: V690D/L692R/L694E/I715K/A717D/M720K/I722D/I761R/I768E/F790D/M796D/L798R/V802E/I816R/G820D/L827E.
