2026/04/28 by Ennio d’Amico, Sami Chaaban, Ferdos Abid Ali +2 · 2 voices
Biochemistry, Genetics and Molecular Biology · Chemistry · Environmental Science · #Bacteriophages and microbial interactions #Bridge (graph theory) #Dynactin #Dynein #Microtubule and mitosis dynamics #Sequence (biology) #Signal transducing adaptor protein #Structural plasticity #Supramolecular Chemistry and Complexes
paper · doi:10.64898/2026.04.25.720804
openalex publication_date 2026/04/28 · openalex created_date 2026/05/02 · openalex updated_date 2026/07/14
Abstract Cargo-specific activating adaptors enable dynein to assemble with dynactin into processive supercomplexes. Adaptors share a coiled-coil architecture, but are highly diverse in sequence and structure, raising the question of how they converge on a common activation mechanism. To address this, we determined near atomic cryo-EM structures of dynein-dynactin assembled with five adaptors: RAB11FIP3, NIN, TRAK1, BICD2 and HOOK3. Despite their heterogeneity, all complexes contain adaptor coiled coils which bridge two dynein dimers to the dynactin filament. Adaptors are defined by an N-terminal interaction at the HBS1 with the dynein heavy chain, additional contacts along the dynein-dynactin groove, and C-terminal binding to the dynactin pointed end. However, we also found distinct sequence features, coiled-coil breaks and pointed-end interfaces that tune complex stoichiometry and stability. Our results define shared principles of dynein activation while revealing unexpected plasticity in how adaptors recognise and organise the dynein-dynactin machinery.