7MGM

Structure of yeast cytoplasmic dynein with AAA3 Walker B mutation bound to Lis1

Summary for 7MGM

• Entry DOI: 10.2210/pdb7mgm/pdb
• EMDB information: 23829
• Descriptor: dynein AAA3-WalkerB mutant (E2488Q), Nuclear distribution protein PAC1, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: motor, aaa, motor protein
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 3
• Total formula weight: 447582.59

Authors

Lahiri, I.,Reimer, J.M.,Leschziner, A.E. (deposition date: 2021-04-12, release date: 2022-01-19, Last modification date: 2024-05-29)

Primary citation

Gillies, J.P.,Reimer, J.M.,Karasmanis, E.P.,Lahiri, I.,Htet, Z.M.,Leschziner, A.E.,Reck-Peterson, S.L.
Structural basis for cytoplasmic dynein-1 regulation by Lis1.
Elife, 11:-, 2022

PubMed Abstract: The lissencephaly 1 gene, , is mutated in patients with the neurodevelopmental disease lissencephaly. The Lis1 protein is conserved from fungi to mammals and is a key regulator of cytoplasmic dynein-1, the major minus-end-directed microtubule motor in many eukaryotes. Lis1 is the only dynein regulator known to bind directly to dynein's motor domain, and by doing so alters dynein's mechanochemistry. Lis1 is required for the formation of fully active dynein complexes, which also contain essential cofactors: dynactin and an activating adaptor. Here, we report the first high-resolution structure of the yeast dynein-Lis1 complex. Our 3.1 Å structure reveals, in molecular detail, the major contacts between dynein and Lis1 and between Lis1's ß-propellers. Structure-guided mutations in Lis1 and dynein show that these contacts are required for Lis1's ability to form fully active human dynein complexes and to regulate yeast dynein's mechanochemistry and in vivo function.

PubMed: 34994688
DOI: 10.7554/eLife.71229

Experimental method

ELECTRON MICROSCOPY (3.1 Å)