Comments on: Structural basis for kinesin-1:cargo recognition.

I evaluated the following article for F1000Prime. The original evaluation is published at . This evaluation has a DOI of 10.3410/f.717995214.793476314

Structural basis for kinesin-1:cargo recognition.
S Pernigo, A Lamprecht, RA Steiner and MP Dodding (2013)
Science 340(6130):356-9
PMID: 23519214
DOI: 10.1126/science.1234264

This paper provides a basis to modulate cargo-motor interactions with a high degree of selectivity. The paper from Dodding and colleagues describes a crystal structure of the tetratricopeptide (TPR)-repeat domain of kinesin light chain (KLC) 2 in association with cargo. Conventional kinesin is a heterotetramer consisting of two each of heavy chain and light chain subunits. Cargo binds to the light chains by virtue of a “tryptophan-acidic motif”.

The new structure was obtained by engineering an in-frame fusion of the cargo, in this case SKIP (SifA-kinesin interacting protein) from the pathogen Salmonella, to the light chain. The structure reveals a number of intriguing features, including an apparent conformational shift in the TPR domain upon cargo binding to enclose the critical tryptophan determinant. This same binding site is also used by a very different cargo, calsyntenin, indicating that this site could serve as a contact site for all kinesin-interacting cargo that displays this tryptophan-acidic motif.

Furthermore, the authors propose a model in which those cargoes, including SKIP, which present two canonical KLC binding motifs might act to bridge the two light chains found in the kinesin tetramer. Such a model immediately proposes a means by which high-affinity cargo binding could transmit a large conformational change through the helical domain of the heavy chain. Further work to determine the validity of this model is clearly a high priority.