Structural basis for kinesin-1:cargo recognition

Science. 2013 Apr 19;340(6130):356-9. doi: 10.1126/science.1234264. Epub 2013 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Glycoproteins / chemistry*
  • Glycoproteins / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Tryptophan / chemistry
  • Tryptophan / genetics
  • Tryptophan / metabolism

Substances

  • Bacterial Proteins
  • Glycoproteins
  • Microtubule-Associated Proteins
  • SifA protein, Salmonella
  • kinesin light-chain proteins
  • Tryptophan

Associated data

  • PDB/3ZFW