AAA+ Ring and linker swing mechanism in the dynein motor.
Dynein ATPases power diverse microtubule-based motilities. Each dynein motor domain comprises a ring-like head containing six AAA+ modules and N- and C-terminal regions, together with a stalk that binds microtubules. How these subdomains are arranged and generate force remains poorly understood. Here, using electron microscopy and image processing of tagged and truncated Dictyostelium cytoplasmic dynein constructs, we show that the heart of the motor is a hexameric ring of AAA+ modules, with the stalk emerging opposite the primary ATPase site (AAA1). The C-terminal region is not an integral part of the ring but spans between AAA6 and near the stalk base. The N-terminal region includes a lever-like linker whose N terminus swings by approximately 17 nm during the ATPase cycle between AAA2 and the stalk base. Together with evidence of stalk tilting, which may communicate changes in microtubule binding affinity, these findings suggest a model for dynein's structure and mechanism.
Roberts
Anthony J
AJ
Astbury Centre for Structural Molecular Biology and Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
Numata
Naoki
N
Walker
Matt L
ML
Kato
Yusuke S
YS
Malkova
Bara
B
Kon
Takahide
T
Ohkura
Reiko
R
Arisaka
Fumio
F
Knight
Peter J
PJ
Sutoh
Kazuo
K
Burgess
Stan A
SA
D000818:Animals; D004023:Dictyostelium / Q000378:metabolism / Q000648:ultrastructure*; D004398:Dyneins / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D015800:Protozoan Proteins / Q000378:metabolism* / Q000648:ultrastructure
D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D004398:Dyneins