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TitleThe hook-like adaptor and cargo-binding (HAC) domain in the kinesin-2 tail enables adaptor assembly and cargo recognition.
Journal, issue, pagesSci Adv, Vol. 11, Issue 43, Page eady5861, Year 2025
Publish dateOct 24, 2025
AuthorsXuguang Jiang / Radostin Danev / Sotaro Ichinose / Baichun Niu / Sumio Ohtsuki / Haruaki Yanagisawa / Satoru Nagatoishi / Kouhei Tsumoto / Nobutaka Hirokawa / Masahide Kikkawa /
PubMed AbstractIntracellular 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 ...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.
External linksSci Adv / PubMed:41134888 / PubMed Central
MethodsEM (single particle)
Resolution2.83 - 2.9 Å
Structure data

65777

9w9h

EMDB-65777, PDB-9w9h:
Cryo-EM structure of the mouse kinesin-2 tail in complex with KAP3 adaptor
Method: EM (single particle) / Resolution: 2.83 Å

65778

9w9i

EMDB-65778, PDB-9w9i:
Cryo-EM structure of the kinesin-2 tail domain in complex with KAP3 and APC
Method: EM (single particle) / Resolution: 2.9 Å

Source
  • mus musculus (house mouse)
KeywordsMOTOR PROTEIN / Kinesin-2 motor Intracellular transport Kinesin-adaptor complex / Kinesin-2 motor Intracellular transport Kinesin-adaptor-cargo complex

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