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TitleLis1 Has Two Opposing Modes of Regulating Cytoplasmic Dynein.
Journal, issue, pagesCell, Vol. 170, Issue 6, Page 1197-1208.e12, Year 2017
Publish dateSep 7, 2017
AuthorsMorgan E DeSantis / Michael A Cianfrocco / Zaw Min Htet / Phuoc Tien Tran / Samara L Reck-Peterson / Andres E Leschziner /
PubMed AbstractRegulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a ...Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here-a combination of biochemistry, single-molecule assays, and cryoelectron microscopy-led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule. We show that these opposing modes depend on the stoichiometry of Lis1 binding to dynein and that this stoichiometry is regulated by the nucleotide state of dynein's AAA3 domain. The low-affinity state requires Lis1 to also bind to dynein at a novel conserved site, mutation of which disrupts Lis1's function in vivo. We propose a new model for the regulation of dynein by Lis1.
External linksCell / PubMed:28886386 / PubMed Central
MethodsEM (single particle)
Resolution7.7 - 10.5 Å
Structure data

EMDB-8673, PDB-5vh9:
Cryo-EM structure of yeast cytoplasmic dynein-1 with Lis1 and ATP
Method: EM (single particle) / Resolution: 7.7 Å

EMDB-8706, PDB-5vlj:
Cryo-EM structure of yeast cytoplasmic dynein with Walker B mutation at AAA3 in presence of ATP-VO4
Method: EM (single particle) / Resolution: 10.5 Å

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsMOTOR PROTEIN / cytoplasmic dynein / lis1

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