7mgm
Structure of yeast cytoplasmic dynein with AAA3 Walker B mutation bound to Lis1
Structural highlights
FunctionDYHC_YEAST Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required to maintain uniform nuclear distribution in hyphae. May play an important role in the proper orientation of the mitotic spindle into the budding daughter cell yeast. Probably required for normal progression of the cell cycle.[1] Publication Abstract from PubMedThe lissencephaly 1 gene, LIS1, 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 A 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. Structural basis for cytoplasmic dynein-1 regulation by Lis1.,Gillies JP, Reimer JM, Karasmanis EP, Lahiri I, Htet ZM, Leschziner AE, Reck-Peterson SL Elife. 2022 Jan 7;11:e71229. doi: 10.7554/eLife.71229. PMID:34994688[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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