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Publication - Dr Mark Dodding

    The light chains of kinesin-1 are autoinhibited

    Citation

    Yip, YY, Pernigo, S, Sanger, A, Xu, M, Parsons, M, Steiner, RA & Dodding, MP, 2016, ‘The light chains of kinesin-1 are autoinhibited’. Proceedings of the National Academy of Sciences of the United States of America, vol 113., pp. 2418-2423

    Abstract

    The light chains (KLCs) of the microtubule motor kinesin-1 bind cargoes and regulate its activity. Through their tetratricopeptide repeat domain (KLC(TPR)), they can recognize short linear peptide motifs found in many cargo proteins characterized by a central tryptophan flanked by aspartic/glutamic acid residues (W-acidic). Using a fluorescence resonance energy transfer biosensor in combination with X-ray crystallographic, biochemical, and biophysical approaches, we describe how an intramolecular interaction between the KLC2(TPR) domain and a conserved peptide motif within an unstructured region of the molecule, partly occludes the W-acidic binding site on the TPR domain. Cargo binding displaces this interaction, effecting a global conformational change in KLCs resulting in a more extended conformation. Thus, like the motor-bearing kinesin heavy chains, KLCs exist in a dynamic conformational state that is regulated by self-interaction and cargo binding. We propose a model by which, via this molecular switch, W-acidic cargo binding regulates the activity of the holoenzyme.

    Full details in the University publications repository