Cryo-ET and MD simulations reveal that dynein-2 is tuned for binding to the A-tubule of the ciliary doublet.

ABSTRACT: Eukaryotic cilia and flagella are thin structures present on the surface of cells, playing vital roles in signaling and cellular motion. Cilia assembly depends on intraflagellar transport (IFT) along doublet microtubules (doublets). Unlike dynein-1, which works on cytoplasmic singlet microtubules, dynein-2 works on the doublets inside cilia. Previous studies have shown that retrograde IFT, driven by dynein-2, occurs on the A-tubule of the doublet, suggesting an elusive mechanism by which dynein-2 recruits retrograde IFT to the A-tubule. Here, we investigated the molecular basis of this mechanism using cryo-electron tomography (cryo-ET), molecular dynamics (MD) simulations, and biochemical analysis. Our biochemical assays revealed that the microtubule-binding domain of dynein-2 exhibits a h

SUBMITTER: He HK 

PROVIDER: S-EPMC12706001 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature