9W9H

Cryo-EM structure of the mouse kinesin-2 tail in complex with KAP3 adaptor

Summary for 9W9H

• Entry DOI: 10.2210/pdb9w9h/pdb
• EMDB information: 65777
• Descriptor: Kinesin-like protein KIF3A, Kinesin-like protein KIF3B, Kinesin-associated protein 3 (3 entities in total)
• Functional Keywords: kinesin-2 motor intracellular transport kinesin-adaptor complex, motor protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 139787.81

Authors

Jiang, X.,Danev, R.,Yanagisawa, H.,Kikkawa, M. (deposition date: 2025-08-10, release date: 2025-10-01, Last modification date: 2025-11-05)

Primary citation

Jiang, X.,Danev, R.,Ichinose, S.,Niu, B.,Ohtsuki, S.,Yanagisawa, H.,Nagatoishi, S.,Tsumoto, K.,Hirokawa, N.,Kikkawa, M.
The hook-like adaptor and cargo-binding (HAC) domain in the kinesin-2 tail enables adaptor assembly and cargo recognition.
Sci Adv, 11:eady5861-eady5861, 2025

PubMed 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.

PubMed: 41134888
DOI: 10.1126/sciadv.ady5861

Experimental method

ELECTRON MICROSCOPY (2.83 Å)