Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
EMBO Rep. 2023 Nov 6;24(11):e56864. doi: 10.15252/embr.202356864. Epub 2023 Aug 14.
Kinesin-driven intracellular transport is essential for various cell biological events and thus plays a crucial role in many pathological processes. However, little is known about the molecular basis of the specific and dynamic cargo-binding mechanism of kinesins. Here, an integrated structural analysis of the KIF3/KAP3 and KIF3/KAP3-APC complexes unveils the mechanism by which KIF3/KAP3 can dynamically grasp APC in a two-step manner, which suggests kinesin-cargo recognition dynamics composed of cargo loading, locking, and release. Our finding is the first demonstration of the two-step cargo recognition and stabilization mechanism of kinesins, which provides novel insights into the intracellular trafficking machinery.
驱动细胞内运输的动力蛋白对于各种细胞生物学事件至关重要，因此在许多病理过程中起着关键作用。然而，对于动力蛋白特定和动态货物结合机制的分子基础知之甚少。在这里，通过对 KIF3/KAP3 和 KIF3/KAP3-APC 复合物的综合结构分析，揭示了 KIF3/KAP3 以两步方式动态抓取 APC 的机制，这表明动力蛋白-货物识别动力学由货物装载、锁定和释放组成。我们的发现首次证明了动力蛋白两步货物识别和稳定机制，为细胞内运输机制提供了新的见解。
