title: ATP-driven remodeling of the linker domain in the dynein motor.
abstract: Dynein ATPases are the largest known cytoskeletal motors and perform critical functions in cells: carrying cargo along microtubules in the cytoplasm and powering flagellar beating. Dyneins are members of the AAA+ superfamily of ring-shaped enzymes, but how they harness this architecture to produce movement is poorly understood. Here, we have used cryo-EM to determine 3D maps of native flagellar dynein-c and a cytoplasmic dynein motor domain in different nucleotide states. The structures show key sites of conformational change within the AAA+ ring and a large rearrangement of the "linker" domain, involving a hinge near its middle. Analysis of a mutant in which the linker "undocks" from the ring indicates that linker remodeling requires energy that is supplied by interactions with the AAA+ modules. Fitting the dynein-c structures into flagellar tomograms suggests how this mechanism could drive sliding between microtubules, and also has implications for cytoplasmic cargo transport.
authors.affiliation: Astbury Centre for Structural Molecular Biology, Institute of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. anthony_roberts@hms.harvard.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: Bara
authors.initials: B
authors.lastname: Malkova
authors.forename: Matt L
authors.initials: ML
authors.lastname: Walker
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakakibara
authors.forename: Naoki
authors.initials: N
authors.lastname: Numata
authors.forename: Takahide
authors.initials: T
authors.lastname: Kon
authors.forename: Reiko
authors.initials: R
authors.lastname: Ohkura
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Edwards
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Knight
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sutoh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Oiwa
authors.forename: Stan A
authors.initials: SA
authors.lastname: Burgess
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry*; D056444:Axonemal Dyneins / Q000737:chemistry* / Q000648:ultrastructure; D054468:Axoneme / Q000648:ultrastructure; D016825:Chlamydomonas reinhardtii / Q000201:enzymology*; D020285:Cryoelectron Microscopy; D004023:Dictyostelium / Q000201:enzymology*; D018715:Microscopy, Video; D008870:Microtubules / Q000737:chemistry / Q000648:ultrastructure; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000648:ultrastructure; D040681:Structural Homology, Protein
chemical_list: D010940:Plant Proteins; D015800:Protozoan Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D056444:Axonemal Dyneins