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Elife. 2018 Oct 15;7. pii: e38362. doi: 10.7554/eLife.38362.

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

Author information

1
Randall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
2
Department of Chemistry, King's College London, London, United Kingdom.
3
School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, United Kingdom.
#
Contributed equally

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.

KEYWORDS:

X-ray crystallography; kinesin-1; molecular biophysics; molecular motor; mouse; structural biology

PMID:
30320553
PMCID:
PMC6214655
DOI:
10.7554/eLife.38362
[Indexed for MEDLINE]
Free PMC Article

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