IFT88-KAP interaction defines a conservedmechanism for kinesin-2-IFT coupling by Guanghan Chen & Zhengyang Guo & Yongping Chai & Wei Li & Guangshuo Ou instant download

IFT88-KAP interaction defines a conservedmechanism for kinesin-2-IFT coupling by Guanghan Chen & Zhengyang Guo & Yongping Chai & Wei Li & Guangshuo Ou instant download

SUMMARYKinesin-2 motors drive intraflagellar transport (IFT) for ciliary assembly, yet the mechanism linking kinesin-2to the IFT machinery has remained elusive. Here, we identify IFT88/OSM-5 as a direct adaptor that recruitskinesin-2 through a conserved electrostatic interface between its tetratricopeptide repeats (TPRs) and thearmadillo (ARM) repeats of the KAP subunit. AlphaFold modeling, mutagenesis, and rescue experiments inC. elegans reveal that a core α7 (IFT88)-α3/α6 (KAP) helical interface is essential for motor engagementand processive IFT, while peripheral contacts are dispensable. Functional conservation of this interfacewas confirmed in human cells, where homologous KAP mutations disrupted ciliary localization. Structuralalignment across species demonstrates evolutionary preservation of the TPR-ARM architecture, suggestingit represents an ancestral module for motor-cargo coupling. These findings define the molecular basis ofkinesin-2/IFT association and establish IFT88-KAP as a conserved hub critical for ciliary assembly andfunction.