Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
- King's College London, United Kingdom
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.
Data availability
Diffraction data and coordinates are publicly available in PDB under the accession codes 6FUZ and 6FV0
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Funding
Biotechnology and Biological Sciences Research Council (BB/L006774/1)
- Soi Bui
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Pernigo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
eLife 7:e38362.
https://doi.org/10.7554/eLife.38362
