The Kinesin-1 C-Terminal Tail is Intrinsically Disordered

Abstract

The C-terminus of kineisn-1 has long been referred to in the literature as the globular tail. In this work we show that this domain is in fact intrinsically disordered. The unfolded structure of the tail domain is revealed via in silico prediction methods, and CD and NMR spectroscopies. It has been well established that a diverse collection of cargos bind exclusively to the tail domain of kinesin-1, and being natively unstructured would allow the tail to sample a variety of conformations in order to accommodate these various binding-partners. Expanding the in silico methods to include other kinesins, we predict that the cargo-binding domains of most members of the human kinesin superfamily are disordered to varying degrees. Therefore, intrinsically disordered sequences may be a general mechanism of cargo binding for many kinesin heavy chains.