Report

Structural Basis for Kinesin-1:Cargo Recognition

Science  19 Apr 2013:
Vol. 340, Issue 6130, pp. 356-359
DOI: 10.1126/science.1234264

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Cargo-Motor Interaction

Kinesin-1 directs a diverse array of functions within axons by interacting with many proteins. To understand the mechanisms underpinning kinesin-cargo recognition, Pernigo et al. (p. 356, published online 21 March) solved the crystal structure of the tetratricopeptide repeat of kinesin light chain 2 bound to a W-acidic cargo peptide from SKIP—a critical host determinant in Salmonella pathogenesis that controls lysosome positioning.

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.

View Full Text