A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome

TY - JOUR

T1 - A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome

AU - Dodding, Mark

AU - Mitter, Richard

AU - Humphries, Ashley C.

AU - Way, Michael

PY - 2011/11/16

Y1 - 2011/11/16

N2 - Transport of cargoes by kinesin-1 is essential for many cellular processes. Nevertheless, the number of proteins known to recruit kinesin-1 via its cargo binding light chain (KLC) is still quite small. We also know relatively little about the molecular features that define kinesin-1 binding. We now show that a bipartite tryptophan-based kinesin-1 binding motif, originally identified in Calsyntenin is present in A36, a vaccinia integral membrane protein. This bipartite motif in A36 is required for kinesin-1-dependent transport of the virus to the cell periphery. Bioinformatic analysis reveals that related bipartite tryptophan-based motifs are present in over 450 human proteins. Using vaccinia as a surrogate cargo, we show that regions of proteins containing this motif can function to recruit KLC and promote virus transport in the absence of A36. These proteins interact with the kinesin light chain outside the context of infection and have distinct preferences for KLC1 and KLC2. Our observations demonstrate that KLC binding can be conferred by a common set of features that are found in a wide range of proteins associated with diverse cellular functions and human diseases. The EMBO Journal (2011) 30, 4523-4538. doi: 10.1038/emboj.2011.326; Published online 13 September 2011

AB - Transport of cargoes by kinesin-1 is essential for many cellular processes. Nevertheless, the number of proteins known to recruit kinesin-1 via its cargo binding light chain (KLC) is still quite small. We also know relatively little about the molecular features that define kinesin-1 binding. We now show that a bipartite tryptophan-based kinesin-1 binding motif, originally identified in Calsyntenin is present in A36, a vaccinia integral membrane protein. This bipartite motif in A36 is required for kinesin-1-dependent transport of the virus to the cell periphery. Bioinformatic analysis reveals that related bipartite tryptophan-based motifs are present in over 450 human proteins. Using vaccinia as a surrogate cargo, we show that regions of proteins containing this motif can function to recruit KLC and promote virus transport in the absence of A36. These proteins interact with the kinesin light chain outside the context of infection and have distinct preferences for KLC1 and KLC2. Our observations demonstrate that KLC binding can be conferred by a common set of features that are found in a wide range of proteins associated with diverse cellular functions and human diseases. The EMBO Journal (2011) 30, 4523-4538. doi: 10.1038/emboj.2011.326; Published online 13 September 2011

U2 - 10.1038/emboj.2011.326

DO - 10.1038/emboj.2011.326

M3 - Article

SN - 0261-4189

VL - 30

SP - 4523

EP - 4538

JO - EMBO Journal

JF - EMBO Journal

IS - 22

ER -