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

TY - JOUR

T1 - 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.

PY - 2018/10/15

Y1 - 2018/10/15

N2 - 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.

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 - kinesin-1

KW - molecular biophysics

KW - molecular motor

KW - mouse

KW - structural biology

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=85056034348&partnerID=8YFLogxK

U2 - 10.7554/eLife.38362

DO - 10.7554/eLife.38362

M3 - Article

C2 - 30320553

AN - SCOPUS:85056034348

SN - 2050-084X

VL - 7

SP - 1

EP - 22

JO - eLife

JF - eLife

ER -