Structural basis for kinesin-1:cargo recognition

DOI: 10.1126/science.1234264
PMID: 23519214

Authors: Stefano Pernigo (King's College London) , Anneri Lamprecht (Kings College London) , Roberto A. Steiner (King's College London) , Mark P. Dodding (King’s College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 340 (6130) , PAGES 356 - 359

State: Published (Approved)
Published: April 2013

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.

Journal Keywords: Amino; Animals; Bacterial; Crystallography; X-Ray; Glycoproteins; HeLa; Humans; Mice; Microtubule-Associated; Mutation; Protein; Secondary; Protein; Tertiary; Tryptophan

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 05/09/2013 15:47

Discipline Tags:

Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)