National Center for
4AKG: Dynein Motor Domain - Atp Complex
Nat. Struct. Mol. Biol. (2012) 19 p.492-497
Dyneins power the beating of cilia and flagella, transport various intracellular cargos and are necessary for mitosis. All dyneins have a approximately 300-kDa motor domain consisting of a ring of six AAA+ domains. ATP hydrolysis in the AAA+ ring drives the cyclic relocation of a motile element, the linker domain, to generate the force necessary for movement. How the linker interacts with the ring during the ATP hydrolysis cycle is not known. Here we present a 3.3-A crystal structure of the motor domain of Saccharomyces cerevisiae cytoplasmic dynein, crystallized in the absence of nucleotides. The linker is docked to a conserved site on AAA5, which is confirmed by mutagenesis as functionally necessary. Nucleotide soaking experiments show that the main ATP hydrolysis site in dynein (AAA1) is in a low-nucleotide affinity conformation and reveal the nucleotide interactions of the other three sites (AAA2, AAA3 and AAA4).