9E10

Dimeric motor domains from phi dynein-1 under Lis1 condition

Summary for 9E10

• Entry DOI: 10.2210/pdb9e10/pdb
• EMDB information: 47374 47379 47381
• Descriptor: Cytoplasmic dynein 1 heavy chain 1, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: dynein-1, phi, motor protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 1069841.29

Authors

Yang, J.,Zhang, K. (deposition date: 2024-10-21, release date: 2025-08-06, Last modification date: 2025-08-13)

Primary citation

Yang, J.,Zhao, Y.,Chai, P.,Yildiz, A.,Zhang, K.
Nde1 promotes Lis1 binding to full-length autoinhibited human dynein 1.
Nat.Chem.Biol., 2025

PubMed Abstract: Cytoplasmic dynein 1 (dynein) is the primary motor responsible for the retrograde transport of intracellular cargoes along microtubules. Activation of dynein requires the opening its autoinhibited Phi conformation, a process driven by Lis1 and Nde1/Ndel1. Using biochemical reconstitution and cryo-electron microscopy, we demonstrate that Nde1 enhances Lis1 binding to autoinhibited dynein and facilitates Phi opening. We identify a key intermediate in this activation pathway where a single Lis1 dimer binds between Phi-like (Phi) motor rings. In this 'Phi-Lis1' complex, Lis1 interacts with one motor domain through canonical sites at the AAA+ (adenosine triphosphatases associated with diverse cellular activities) ring and stalk, and with AAA5, AAA6 and linker regions of the other motor domain. Mutagenesis and motility assays confirm the critical role of the Phi-Lis1 interface in dynein activation. This intermediate forms rapidly in the presence of Nde1, although Nde1 is not part of Phi-Lis1. These findings provide key insights into how Nde1 promotes Lis1-mediated Phi opening.

PubMed: 40751002
DOI: 10.1038/s41589-025-01981-6

Experimental method

ELECTRON MICROSCOPY (2.71 Å)