Fig. 6: Classification of dynein–dynactin adaptors into three subfamilies with different LIC1 interactions.

a–c Residues L444, L451, F447, and F448 (bold) on the hydrophobic side of the LIC1 helix insert into a hydrophobic cleft in all the adaptors, which use different folds and different protein–protein contacts to binds this helix (see also Supplementary Fig. 6): CC1-box (magenta), EF-hand pair (orange), and HOOK domain (dark green). Based on this interaction, the adaptors fall into three subfamilies, each containing several members with different domain architectures (for a complete list see Supplemental Table 1). C-terminal to the LIC1-binding site, all the adaptors present a coiled-coil segment (striped cyan) that binds the dynactin actin-like filament and provides part of the binding interface for the dynein tails^5,9,12. C-terminal to the dynactin-binding coiled-coil, the adaptors have the Spindly motif (light green) that interacts with subunits p25/p27 at the pointed end of the dynactin complex (see also Supplementary Fig. 5). d Schematic representation of the LIC1–adaptor interaction within the context of dynein–dynactin–adaptor complexes. A prototypical adaptor is depicted (cyan), showing the variable (tunable) interaction with the LIC1 helix near CapZαβ at the barbed end of the dynactin filament, the coiled-coil segment that binds dynein–dynactin, and the Spindly motif. C-terminal to the Spindly motif the adaptors differ the most. This variable region is directly or indirectly responsible for the recruitment of specific cargoes. e Members of the RILP and JIP family share some features with the dynein–dynactin adaptors, including the ability to bind LIC1, but are unlikely to activate processive motility¹.