8QAT

Cryo-EM structure of Fts-Hook3-FHIP1B at 3.2 A resolution.

Summary for 8QAT

• Entry DOI: 10.2210/pdb8qat/pdb
• EMDB information: 18302
• Descriptor: Protein Hook homolog 3, FHF complex subunit HOOK-interacting protein 1B, AKT-interacting protein (3 entities in total)
• Functional Keywords: motor proteins ; molecular motors ; cargo adaptors ; bidirectional transport ; microtubules ; cytoskeleton., protein transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 173605.62

Authors

Abid Ali, F.,Carter, A.P. (deposition date: 2023-08-23, release date: 2024-09-04, Last modification date: 2025-04-23)

Primary citation

Abid Ali, F.,Zwetsloot, A.J.,Stone, C.E.,Morgan, T.E.,Wademan, R.F.,Carter, A.P.,Straube, A.
KIF1C activates and extends dynein movement through the FHF cargo adapter.
Nat.Struct.Mol.Biol., 32:756-766, 2025

PubMed Abstract: Cellular cargos move bidirectionally on microtubules by recruiting opposite polarity motors dynein and kinesin. These motors show codependence, where one requires the activity of the other, although the mechanism is unknown. Here we show that kinesin-3 KIF1C acts as both an activator and a processivity factor for dynein, using in vitro reconstitutions of human proteins. Activation requires only a fragment of the KIF1C nonmotor stalk binding the cargo adapter HOOK3. The interaction site is separate from the constitutive factors FTS and FHIP, which link HOOK3 to small G-proteins on cargos. We provide a structural model for the autoinhibited FTS-HOOK3-FHIP1B (an FHF complex) and explain how KIF1C relieves it. Collectively, we explain codependency by revealing how mutual activation of dynein and kinesin occurs through their shared adapter. Many adapters bind both dynein and kinesins, suggesting this mechanism could be generalized to other bidirectional complexes.

PubMed: 39747486
DOI: 10.1038/s41594-024-01418-z

Experimental method

ELECTRON MICROSCOPY (3.2 Å)