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Insights into dynein motor domain function from a 3.3-Å crystal structure

DOI: 10.1038/nsmb.2272 DOI Help
PMID: 22426545 PMID Help

Authors: Helgo Schmidt (Medical Research Council Laboratory of Molecular Biology) , Emma S. Gleave (Medical Research Council Laboratory of Molecular Biology) , Andrew P. Carter (Medical Research Council Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology

State: Published (Approved)
Published: March 2012
Diamond Proposal Number(s): 8547

Abstract: Dyneins power the beating of cilia and flagella, transport various intracellular cargos and are necessary for mitosis. All dyneins have a ?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-Å 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).

Journal Keywords: Binding; Crystallography; X-Ray; Dyneins; Fungal; Models; Molecular; Nucleotides; Protein; Tertiary; Saccharomyces cerevisiae

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography

Other Facilities: ESRF