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TitleStructural basis for cytoplasmic dynein-1 regulation by Lis1.
Journal, issue, pagesElife, Vol. 11, Year 2022
Publish dateJan 7, 2022
AuthorsJohn P Gillies / Janice M Reimer / Eva P Karasmanis / Indrajit Lahiri / Zaw Min Htet / Andres E Leschziner / Samara L Reck-Peterson /
PubMed AbstractThe 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- ...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.
External linksElife / PubMed:34994688 / PubMed Central
MethodsEM (single particle)
Resolution3.02 - 3.1 Å
Structure data

EMDB-23829, PDB-7mgm:
Structure of yeast cytoplasmic dynein with AAA3 Walker B mutation bound to Lis1
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-25497:
Signal-subtracted reconstruction of yeast cytoplasmic dynein-1 (AAA3 Walker B mutant, E2488Q) AAA2-AAA5L domains bound to Lis1
Method: EM (single particle) / Resolution: 3.02 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-MG:
Unknown entry

Source
  • saccharomyces cerevisiae (baker's yeast)
  • baker's yeast (baker's yeast)
KeywordsMOTOR PROTEIN / motor / AAA

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