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

Authors
Lee, In-GyunCason, Sydney E.Alqassim, Saif S.Holzbaur, Erika L. F.Dominguez, Roberto
Issue Date
2020-11
Publisher
Nature Publishing Group
Citation
Nature Communications, v.11, no.1
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 mu M. We propose that a tunable LIC1-adaptor interaction modulates dynein's motility in a cargo-specific manner. Activating adaptors that link dynein to its general cofactor dynactin recruit specific cargoes and regulate dynein's activity and processive motility in retrograde transport. Here, the authors present the crystal structures of two adaptor complexes with the dynein light intermediate chain-1 (LIC1) and show that activating adaptors can be grouped into three structural classes based on their different interactions with LIC1.
Keywords
CYTOPLASMIC DYNEIN; DYNACTIN RECRUITS; STRUCTURAL BASIS; ACTIVATION; PROTEINS; MOTILITY; SEQUENCE; REVEALS; CALCIUM; COMPLEX; Dynein; X-ray crystallography
ISSN
2041-1723
URI
https://pubs.kist.re.kr/handle/201004/117902
DOI
10.1038/s41467-020-19538-7
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KIST Article > 2020
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