A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity

Nat Commun. 2018 Mar 7;9(1):986. doi: 10.1038/s41467-018-03412-8.


Cytoplasmic dynein is the major minus-end-directed microtubule-based motor in cells. Dynein processivity and cargo selectivity depend on cargo-specific effectors that, while generally unrelated, share the ability to interact with dynein and dynactin to form processive dynein-dynactin-effector complexes. How this is achieved is poorly understood. Here, we identify a conserved region of the dynein Light Intermediate Chain 1 (LIC1) that mediates interactions with unrelated dynein-dynactin effectors. Quantitative binding studies map these interactions to a conserved helix within LIC1 and to N-terminal fragments of Hook1, Hook3, BICD2, and Spindly. A structure of the LIC1 helix bound to the N-terminal Hook domain reveals a conformational change that creates a hydrophobic cleft for binding of the LIC1 helix. The LIC1 helix competitively inhibits processive dynein-dynactin-effector motility in vitro, whereas structure-inspired mutations in this helix impair lysosomal positioning in cells. The results reveal a conserved mechanism of effector interaction with dynein-dynactin necessary for processive motility.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Cytoplasmic Dyneins / chemistry
  • Cytoplasmic Dyneins / metabolism*
  • Dynactin Complex / metabolism
  • HeLa Cells
  • Humans
  • Movement
  • Protein Conformation


  • Dynactin Complex
  • DYNC1LI1 protein, human
  • Cytoplasmic Dyneins