title: 25 Angstrom resolution structure of a cytoplasmic dynein motor reveals a seven-member planar ring.
abstract: Dyneins form one of the three major families of cytoskeleton-based motor proteins that together drive most of the visible forms of cell and organelle movement. We present here a 3D reconstruction of a cytoplasmic dynein motor domain obtained by electron microscopy, at 25 Angstrom resolution. This work demonstrates a basic motor architecture of a flat, slightly elliptical ring composed of seven densities arranged around a partially enclosed central cavity. We have used specific Fab tags to localize the microtubule-binding domain; the connecting stalk emerges at one end of the motor's long axis. Through proposed fitting of representative AAA domain structures, we show that the nucleotide catalytic P-1 domain is likely located at the opposite end of the motor. Thus mechanisms that couple nucleotide hydrolysis with microtubule binding must be propagated around a ring structure, in a manner clearly distinct from kinesin or myosin-mediated movements. Analysis of the Fab tagged datasets reveals classes of particles with stalks protruding at distinct angles from the motor. There is a approximately 40 degrees variation in microtubule-binding stalk angle that may reflect linkage to dynein's mechanochemical cycle. Overall, the work provides sufficient resolution to begin the mapping of landmark features onto a dynein motor, and provides a foundation for understanding the mechanics of dynein movement.
authors.affiliation: Division of Molecular Medicine Wadsworth Center, Empire State Plaza, PO Box 509, Albany, NY 12201-0509, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Samsó
authors.forename: Michael P
authors.initials: MP
authors.lastname: Koonce
mesh_terms: D000906:Antibodies / Q000276:immunology; D003593:Cytoplasm; D004398:Dyneins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D000906:Antibodies; D004398:Dyneins