期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.71229
关键词
dynein; Lis1; BicD2; dynactin; hook3; Human; S; cerevisiae
类别
资金
- Howard Hughes Medical Institute
- National Institutes of Health [R35 GM141825, R01 GM107214, T32 GM008326]
- Damon Runyon Cancer Research Foundation [DRG-2370-19]
- Jane Coffin Childs Memorial Fund for Medical Research
We report the high-resolution structure of the yeast dynein-Lis1 complex, which reveals 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.
The 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 angstrom 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.
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