title: Structural basis for kinesin-1:cargo recognition.
abstract: Kinesin-mediated cargo transport is required for many cellular functions and plays a key role in pathological processes. Structural information on how kinesins recognize their cargoes is required for a molecular understanding of this fundamental and ubiquitous process. Here, we present the crystal structure of the tetratricopeptide repeat domain of kinesin light chain 2 in complex with a cargo peptide harboring a "tryptophan-acidic" motif derived from SKIP (SifA-kinesin interacting protein), a critical host determinant in Salmonella pathogenesis and a regulator of lysosomal positioning. Structural data together with biophysical, biochemical, and cellular assays allow us to propose a framework for intracellular transport based on the binding by kinesin-1 of W-acidic cargo motifs through a combination of electrostatic interactions and sequence-specific elements, providing direct molecular evidence of the mechanisms for kinesin-1:cargo recognition.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pernigo
authors.forename: Anneri
authors.initials: A
authors.lastname: Lamprecht
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Steiner
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dodding
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006023:Glycoproteins; C000715691:Klc2 protein, mouse; D008869:Microtubule-Associated Proteins; C421862:SifA protein, Salmonella; D014364:Tryptophan; D016547:Kinesins