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

Lee, In-Gyun; Cason, Sydney E.; Alqassim, Saif S.; Holzbaur, Erika L.  F.; Dominguez, Roberto

doi:10.1038/s41467-020-19538-7

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

Journal Article · Mon Nov 09 23:00:00 EST 2020 · Nature Communications

DOI:https://doi.org/10.1038/s41467-020-19538-7· OSTI ID:1817091

Lee, In-Gyun ^[1]; Cason, Sydney E. ^[2]; ^[3]; ^[2]; ^[3]

Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine. Dept. of Physiology and Pennsylvania Muscle Inst.; OSTI
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine. Dept. of Physiology and Pennsylvania Muscle Inst.; Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine. Biomedical Graduate Studies. Neuroscience Graduate Group
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine. Dept. of Physiology and Pennsylvania Muscle Inst.

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.

View Accepted Manuscript (DOE)

Research Organization:: Stanford Univ., CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1817091

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 11; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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