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.
Original language | English |
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Pages (from-to) | 356-9 |
Number of pages | 4 |
Journal | Science |
Volume | 340 |
Issue number | 6130 |
DOIs | |
Publication status | Published - 19 Apr 2013 |
Keywords
- Amino Acid Motifs
- Amino Acid Sequence
- Animals
- Bacterial Proteins
- Crystallography, X-Ray
- Glycoproteins
- HeLa Cells
- Humans
- Mice
- Microtubule-Associated Proteins
- Molecular Sequence Data
- Mutation
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Tryptophan
- Journal Article
- Research Support, Non-U.S. Gov't