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A tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner

Author

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  • In-Gyun Lee

    (University of Pennsylvania
    Korea Institute of Science and Technology (KIST))

  • Sydney E. Cason

    (University of Pennsylvania
    University of Pennsylvania)

  • Saif S. Alqassim

    (University of Pennsylvania
    Mohammed Bin Rashid University of Medicine and Health Sciences)

  • Erika L. F. Holzbaur

    (University of Pennsylvania
    University of Pennsylvania)

  • Roberto Dominguez

    (University of Pennsylvania)

Abstract

Cytoplasmic dynein-1 (dynein) is the motor responsible for most retrograde transport of cargoes along microtubules in eukaryotic cells, including organelles, mRNA and viruses. Cargo selectivity and activation of processive motility depend on a group of so-called “activating adaptors” that link dynein to its general cofactor, dynactin, and cargoes. The mechanism by which these adaptors regulate dynein transport is poorly understood. Here, based on crystal structures, quantitative binding studies, and in vitro motility assays, we show that BICD2, CRACR2a, and HOOK3, representing three subfamilies of unrelated adaptors, interact with the same amphipathic helix of the dynein light intermediate chain-1 (LIC1). While the hydrophobic character of the interaction is conserved, the three adaptor subfamilies use different folds (coiled-coil, EF-hand, HOOK domain) and different surface contacts to bind the LIC1 helix with affinities ranging from 1.5 to 15.0 μM. We propose that a tunable LIC1-adaptor interaction modulates dynein’s motility in a cargo-specific manner.

Suggested Citation

  • In-Gyun Lee & Sydney E. Cason & Saif S. Alqassim & Erika L. F. Holzbaur & Roberto Dominguez, 2020. "A tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19538-7
    DOI: 10.1038/s41467-020-19538-7
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