TY - JOUR TI - Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors AU - Pernigo, Stefano AU - Chegkazi, Magda S AU - Yip, Yan Y AU - Treacy, Conor AU - Glorani, Giulia AU - Hansen, Kjetil AU - Politis, Argyris AU - Bui, Soi AU - Dodding, Mark P AU - Steiner, Roberto A A2 - Reck-Peterson, Samara L A2 - Musacchio, Andrea VL - 7 PY - 2018 DA - 2018/10/15 SP - e38362 C1 - eLife 2018;7:e38362 DO - 10.7554/eLife.38362 UR - https://doi.org/10.7554/eLife.38362 AB - 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. KW - molecular motor KW - kinesin-1 KW - X-ray crystallography JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -