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bioRxiv · 10.1101/2023.12.24.573241

The FHA domain is essential for the autoinhibition of KIF1A/UNC-104

Niwa, S.·Watanabe, T.·Chiba, K.
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Abstract

KIF1A/UNC-104, a member of the kinesin super family motor proteins, plays a pivotal role in the axonal transport of synaptic vesicles and their precursors. Drosophila melanogaster UNC-104 (DmUNC-104) is a relatively recently discovered Drosophila kinesin. Although some point mutations that disrupt synapse formation have been identified, the biochemical properties of DmUNC-104 protein have not been investigated. Here, we prepared recombinant full-length DmUNC-104 protein and determined the biochemical features. We analyzed the effect of a previously identified missense mutation in the FHA domain, called bristly (bris), and found that wild-type DmUNC-104 is a mixture of monomer and dimer and the bris mutation strongly promote the dimerization. Furthermore, we found that disease-associated mutations also promote the dimerization of DmUNC-104. These findings suggest that the FHA domain is essential for the autoinhibition of KIF1A/UNC-104, and that abnormal dimerization of KIF1A is linked to human diseases.

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Niwa, S., Watanabe, T., Chiba, K.. 2023-12-24. The FHA domain is essential for the autoinhibition of KIF1A/UNC-104. https://doi.org/10.1101/2023.12.24.573241

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