Browse/search for people

Publication - Dr Mark Dodding

    Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors

    Citation

    Pernigo, S, Chegkazi, MS, Yip, YY, Treacy, C, Glorani, G, Hansen, K, Politis, A, Bui, S, Dodding, MP & Steiner, RA, 2018, ‘Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors’. eLife, vol 7.

    Abstract

    The light chains (KLCs) of the heterotetrameric microtubule motor
    kinesin-1, that bind to cargo adaptor proteins and regulate its
    activity, have a capacity to recognize short peptides via their
    tetratricopeptide repeat domains (KLCTPR). Here, using X-ray
    crystallography, we show how kinesin-1 recognizes a novel class of
    adaptor motifs that we call 'Y-acidic' (tyrosine flanked by acidic
    residues), in a KLC-isoform specific manner. Binding specificities of
    Y-acidic motifs (present in JIP1 and in TorsinA) to KLC1TPR
    are distinct from those utilized for the recognition of W-acidic motifs
    found in adaptors that are KLC- isoform non-selective. However, a
    partial overlap on their receptor binding sites implies that adaptors
    relying on Y-acidic and W-acidic motifs must act independently. We
    propose a model to explain why these two classes of motifs that bind to
    the concave surface of KLCTPR with similar low micromolar affinity can exhibit different capacities to promote kinesin-1 activity.

    Full details in the University publications repository