5vlj | pdb_00005vlj
Cryo-EM structure of yeast cytoplasmic dynein with Walker B mutation at AAA3 in presence of ATP-VO4
Structural highlights
Function[DYHC_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] [LIS1_YEAS7] Positively regulates the activity of the minus-end directed microtubule motor protein dynein. Plays a central role in positioning the mitotic spindle at the bud neck during cell division. Targets cytoplasmic dynein to microtubule plus ends, thereby promoting dynein-mediated microtubule sliding along the bud cortex and consequently the movement of the mitotic spindle to the bud neck. Publication Abstract from PubMedRegulation 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. Lis1 Has Two Opposing Modes of Regulating Cytoplasmic Dynein.,DeSantis ME, Cianfrocco MA, Htet ZM, Tran PT, Reck-Peterson SL, Leschziner AE Cell. 2017 Sep 7;170(6):1197-1208.e12. doi: 10.1016/j.cell.2017.08.037. PMID:28886386[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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