Structural Basis for Kinesin-1:Cargo Recognition

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 s...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-04, Vol.340 (6130), p.356-359
Main Authors: Pernigo, Stefano, Lamprecht, Anneri, Steiner, Roberto A., Dodding, Mark P.
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Amino acids
Animals
Arrays
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Carboxylates
Chains
Crystal structure
Crystallography, X-Ray
Determinants
Electrostatics
Freight
Freight transport
Glycoproteins - chemistry
Glycoproteins - metabolism
HeLa Cells
Humans
Hydrogen bonds
Lysosomes
Mice
Microtubule-Associated Proteins - chemistry
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Molecular biology
Molecular Sequence Data
Mutation
Pathogenesis
Peptides
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins
Recognition
Research fellowships
Salmonella
Tryptophan - chemistry
Tryptophan - genetics
Tryptophan - metabolism
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1234264