Abstract
Kif7, a member of the kinesin 4 superfamily, is implicated inavariety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may playa role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melanogaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance.
Highlights
Members of the kinesin superfamily of motor proteins (Kifs) move unidirectionally along microtubules (MTs) in an ATPdependent manner
In our effort to characterize human kinesins of medical interest, we report here the crystal structure of the human Kif7 motor domain to 1.6 Aresolution
Codon-optimized cDNAs for Kif78–361 and Kif271–341 were purchased from GenScript and cloned into a modified pETM20 Escherichia coli expression vector carrying an N-terminal Trx-fusion protein, a His tag and a TEV cleavage site
Summary
Members of the kinesin superfamily of motor proteins (Kifs) move unidirectionally along microtubules (MTs) in an ATPdependent manner. Human Kif and Kif, which are members of the kinesin-4 family (Katoh & Katoh, 2004a,b), are paralogues They share 44% sequence identity overall and have even higher identity in the motor domain (61%). They possess an N-terminal globular motor domain that contains nucleotide-binding and MT-interacting regions, followed by a stalk domain predicted to form a discontinuous coiled coil and a globular C-terminal tail domain (Fig. 1) Both proteins are orthologues of the Drosophila melanogaster kinesin-like protein called Costal-2 (Cos2) that plays a key role in Hedgehog (Hh) signalling. In our effort to characterize human kinesins of medical interest, we report here the crystal structure of the human Kif motor domain to 1.6 Aresolution We compare this crystal structure with that of the founding member of the kinesin superfamily, conventional kinesin (kinesin-1 family). This is the first step towards the structural characterization of a kinesin-4 family member
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
