title: A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.
abstract: Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge CB2 0QH, UK.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Gleave
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge CB2 0QH, UK.
authors.forename: Helgo
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge CB2 0QH, UK. Electronic address: cartera@mrc-lmb.cam.ac.uk.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Carter
mesh_terms: D000595:Amino Acid Sequence; D056445:Cytoplasmic Dyneins / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D056445:Cytoplasmic Dyneins
keywords: ATPases Associated with diverse cellular Activities (AAA+); Coiled-coil; Cytoskeleton; Dynein; Microtubule; Motor protein