Lee, In-Gyun Cason, Sydney E. Alqassim, Saif S. Holzbaur, Erika L. F. Dominguez, Roberto 2024-01-19T16:04:38Z 2024-01-19T16:04:38Z 2021-09-02 2020-11 2041-1723 https://pubs.kist.re.kr/handle/201004/117902 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. English Nature Publishing Group A tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner Article 10.1038/s41467-020-19538-7 1 Nature Communications, v.11, no.1 Nature Communications 11 1 Y scie scopus 000593978400010 2-s2.0-85095736056 Multidisciplinary Sciences Science & Technology - Other Topics Article CYTOPLASMIC DYNEIN DYNACTIN RECRUITS STRUCTURAL BASIS ACTIVATION PROTEINS MOTILITY SEQUENCE REVEALS CALCIUM COMPLEX Dynein X-ray crystallography