A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. 2018

In-Gyun Lee, and Mara A Olenick, and Malgorzata Boczkowska, and Clara Franzini-Armstrong, and Erika L F Holzbaur, and Roberto Dominguez
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Cytoplasmic dynein is the major minus-end-directed microtubule-based motor in cells. Dynein processivity and cargo selectivity depend on cargo-specific effectors that, while generally unrelated, share the ability to interact with dynein and dynactin to form processive dynein-dynactin-effector complexes. How this is achieved is poorly understood. Here, we identify a conserved region of the dynein Light Intermediate Chain 1 (LIC1) that mediates interactions with unrelated dynein-dynactin effectors. Quantitative binding studies map these interactions to a conserved helix within LIC1 and to N-terminal fragments of Hook1, Hook3, BICD2, and Spindly. A structure of the LIC1 helix bound to the N-terminal Hook domain reveals a conformational change that creates a hydrophobic cleft for binding of the LIC1 helix. The LIC1 helix competitively inhibits processive dynein-dynactin-effector motility in vitro, whereas structure-inspired mutations in this helix impair lysosomal positioning in cells. The results reveal a conserved mechanism of effector interaction with dynein-dynactin necessary for processive motility.

UI MeSH Term Description Entries
D009068 Movement The act, process, or result of passing from one place or position to another. It differs from LOCOMOTION in that locomotion is restricted to the passing of the whole body from one place to another, while movement encompasses both locomotion but also a change of the position of the whole body or any of its parts. Movement may be used with reference to humans, vertebrate and invertebrate animals, and microorganisms. Differentiate also from MOTOR ACTIVITY, movement associated with behavior. Movements
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072159 Dynactin Complex A multi-subunit protein of EUKARYOTIC CELLS. It functions in bidirectional intracellular transport of ORGANELLES and CYTOPLASMIC VESICLES by linking them to DYNEIN and KINESIN. 150 kDa Dynein-Associated Protein,Dynactin,Dynactin 1,Dynactin Subunit 1,Dynactin Subunit 2,Dynactin Subunit 3,Dynactin Subunit 4,Dynactin-2,Dynactin-3,Dynactin-4,Dynactins,Dynamitin Protein,Dynein Activator Protein,Dynein-Associated Protein, 150-kDa,p150(Glued),p22 Dynactin Light Chain,p50 Dynamitin,150 kDa Dynein Associated Protein,150-kDa Dynein-Associated Protein,Dynactin 2,Dynactin 3,Dynactin 4,Dynamitin, p50,Dynein Associated Protein, 150 kDa
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D056445 Cytoplasmic Dyneins Dyneins that are responsible for intracellular transport, MITOSIS, cell polarization, and movement within the cell. Cytoplasmic Dynein,Dynein, Cytoplasmic,Dyneins, Cytoplasmic

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