細胞の“運び屋”に新たなルール～脳の働きや病気の理解につながるタンパク質輸送の仕組み～

2025-10-25 東京大学,順天堂大学,群馬大学

細胞の“運び屋” キネシン‐2が荷物を見分けて運ぶしくみ

<関連情報>

• https://www.u-tokyo.ac.jp/content/400273106.pdf
• https://www.science.org/doi/10.1126/sciadv.ady5861

キネシン2の尾部にあるフック状のアダプターと貨物結合(HAC)ドメインは、アダプターの組み立てと貨物の認識を可能にする The hook-like adaptor and cargo-binding (HAC) domain in the kinesin-2 tail enables adaptor assembly and cargo recognition

Xuguang Jiang, Radostin Danev, Sotaro Ichinose, Baichun Niu, […] , and Masahide Kikkawa
Science Advances  Published:24 Oct 2025
DOI:https://doi.org/10.1126/sciadv.ady5861

Abstract

Intracellular transport relies on motor proteins such as kinesins to deliver cargo along microtubules, yet how they recognize cargo remains unclear. Here, we present high-resolution cryo–electron microscopy structures of the heterotrimeric kinesin-2 complex (KIF3A/KIF3B/KAP3) bound to the cargo protein APC. Our findings reveal a previously uncharacterized KIF3 tail hook-like motif, termed the “HAC” domain, which mediates binding to both KAP3 adaptor and APC cargo. Within this domain, the KIF3A helical regions ensure cargo specificity, while a β-hairpin and KIF3B provide structural support. Biochemical and neuronal experiments confirm its functional importance. Notably, the HAC/KAP3 structure resembles hook-like architectures seen in kinesin-1 and dynein, suggesting a shared cargo recognition framework. These findings also shed light on kinesin-2 cargo specificity and offer a structural framework for understanding related neuronal transport mechanisms.