9BLY

Composite structure of full-length human dynein-1 in phi-particle conformation

This is a non-PDB format compatible entry.

Summary for 9BLY

• Entry DOI: 10.2210/pdb9bly/pdb
• EMDB information: 44681
• Descriptor: Cytoplasmic dynein 1 heavy chain 1, Cytoplasmic dynein 1 intermediate chain 2, Cytoplasmic dynein 1 light intermediate chain 2, ... (9 entities in total)
• Functional Keywords: dynein-1, phi-particle, motor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 1388837.43

Authors

Chai, P.,Zhang, K. (deposition date: 2024-05-02, release date: 2025-04-23, Last modification date: 2025-04-30)

Primary citation

Chai, P.,Yang, J.,Geohring, I.C.,Markus, S.M.,Wang, Y.,Zhang, K.
The mechanochemical cycle of reactive full-length human dynein 1.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Dynein-driven cargo transport has a pivotal role in diverse cellular activities, central to which is dynein's mechanochemical cycle. Here, we performed a systematic cryo-electron microscopic investigation of the conformational landscape of full-length human dynein 1 in reaction, in various nucleotide conditions, on and off microtubules. Our approach reveals over 40 high-resolution structures, categorized into eight states, providing a dynamic and comprehensive view of dynein throughout its mechanochemical cycle. The described intermediate states reveal mechanistic insights into dynein function, including a 'backdoor' phosphate release model that coordinates linker straightening, how microtubule binding enhances adenosine triphosphatase activity through a two-way communication mechanism and the crosstalk mechanism between AAA1 and the regulatory AAA3 site. Our findings also lead to a revised model for the force-generating powerstroke and reveal means by which dynein exhibits unidirectional stepping. These results improve our understanding of dynein and provide a more complete model of its mechanochemical cycle.

PubMed: 40263469
DOI: 10.1038/s41594-025-01543-3

Experimental method

ELECTRON MICROSCOPY (3.5 Å)