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. 2022 Nov 21;5:25152564221134328. doi: 10.1177/25152564221134328

Figure 1.

Figure 1.

Five families of bridge-like lipid transfer proteins contain from 6 to 17 RBG domains.

A. Domain structure in five families of eukaryotic bridge-like lipid transfer proteins. Repeating beta-groove (RBG) domains (yellow, also called “extended chorein-N domains” (Melia and Reinisch, 2022)) are numbered below. Also showing previously known domains with non-RBG structure: VAB repeats (VPS13 only, dark green), α repeats - tandem repeats (∼75 aa each) of paired helices in VPS13 and ATG2, also called ATG_C domains (magenta), pleckstrin homology (PH) domain in VPS13 (sky-blue), and transmembrane helices (TMH, black) (Tweek and Hobbit). An intrinsically disordered loop >300 residues long in SHIP164 is also indicated (Hanna et al., 2022), but loops shorter than 100 aa are not indicated. Blue regions A and B near the N-terminus of VPS13 (64-300 and 690-827) indicate bands where mutating hydrophobic sidechains lining the groove to charged residues (11 and 16 respectively) inhibited VPS13 function without altering the fold (Li et al., 2020). Predicted lengths of the RBG structures are as published elsewhere (Guillén-Samander et al., 2022; Neuman et al., 2022b). Homologs chosen are from yeast where possible (Vps13, Atg2, Csf1 and Hob1/Fmp27), as they are the most compact and have the smallest additional intrinsically disordered loops, or from human (SHIP164/UHRF1BP1L). B. Cartoon of three repeating β-groove (RBG) domains (colored blue/green/yellow in series). Each RBG domain consists of five β-strands in a meander pattern followed by the final sixth element consisting of an intrinsically disordered loop that most often starts with a short helix. Adapted from Neuman et al. (2022b) with permission. C. Structure of RBG domains 3, 4 and 5 from human Hobbit/BLTP2 (KIAA0100, residues 272-729) predicted by AlphaFold, colored as in B. D. Surface of RBG5 from C. (residues 569-695) showing the inside (concave) surface has hydrophobic side-chains (brown), while the outside (convex) surface is populated with hydrophilic side-chains (blue).