title: A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome.
abstract: 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.
authors.affiliation: Cell Motility Laboratory, London Research Institute, Cancer Research UK, London, UK.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dodding
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Humphries
authors.forename: Michael
authors.initials: M
authors.lastname: Way
mesh_terms: D020816:Amino Acid Motifs; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D015894:Genome, Human; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014364:Tryptophan / Q000737:chemistry; D014616:Vaccinia virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release
chemical_list: C503225:CLSTN1 protein, human; D002135:Calcium-Binding Proteins; C488101:KIF5B protein, human; C000715688:KLC1 protein, human; D008869:Microtubule-Associated Proteins; D014763:Viral Matrix Proteins; D014364:Tryptophan; D016547:Kinesins