6pse | pdb_00006pse
Complex of BICD2 with a Dynein Light Intermediate Chain Peptide
Structural highlights
DiseaseBICD2_HUMAN BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy. The disease is caused by mutations affecting the gene represented in this entry. FunctionBICD2_HUMAN Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates and stabilizes the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (By similarity). Facilitates the binding of RAB6A to the Golgi by stabilizing its GTP-bound form. Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport via its interaction with RAB6A and recruitment of the dynein-dynactin motor complex (PubMed:25962623). Contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1. During G2 phase of the cell cycle, associates with RANBP2 at the nuclear pores and recruits dynein and dynactin to the nuclear envelope to ensure proper positioning of the nucleus relative to centrosomes prior to the onset of mitosis (By similarity).[UniProtKB:Q921C5][1] Publication Abstract from PubMedCytoplasmic 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 muM. We propose that a tunable LIC1-adaptor interaction modulates dynein's motility in a cargo-specific manner. A tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner.,Lee IG, Cason SE, Alqassim SS, Holzbaur ELF, Dominguez R Nat Commun. 2020 Nov 10;11(1):5695. doi: 10.1038/s41467-020-19538-7. PMID:33173051[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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