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

DOI: 10.7554/eLife.38362 DOI Help

Authors: Stefano Pernigo (King's College London) , Magda S. Chegkazi (King's College London) , Yan Y. Yip (King’s College London) , Conor Treacy (King's College London) , Giulia Glorani (King’s College London) , Kjetil Hansen (King’s College London) , Argyris Politis (King’s College London) , Soi Bui (King's College London) , Mark P. Dodding (King’s College London; University of Bristol) , Roberto A. Steiner (King's College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 7

State: Published (Approved)
Published: October 2018

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Other Facilities: Petra III/DESY

Documents:
elife-38362-v3.pdf

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