Does axonemal dynein push, pull, or oscillate?
Dynein is the molecular motor that provides motive force in cilia and flagella. Dynein is anchored to the A-subtubule of the outer doublets by a club-shaped extension called the stem, which supports the large globular head of the molecule. Dynein forms an attachment or cross-bridge to the B-subtubule of the adjacent outer doublet through a slender appendage extending from the head that is called the stalk or alternately the B-link. It is generally thought that the B-link mediates the interdoublet transfer of force that bends the flagellum. This requires that energy released at the site of ATP hydrolysis, located in the globular head, be transferred as mechanical work to the microtubule binding site at the tip of the B-link. It has been proposed that this is accomplished by a sideways or rotational translocation of the B-link caused by a rotation of the globular head. An estimate of the stiffness of the B-link and stem derived from the recently published data of Burgess et al. [2003: Nature 421:715-718] yields a maximum stiffness of 0.47 pN/nm for the B-link and 0.1 pN/nm for the stem. The B-link stiffness would allow transfer of 3.8 pN of force in response to an 8-nm displacement of the B-link tip. However, if as proposed the globular head of the dynein heavy chain is supported by the stem, the B-link and stem elasticity are in series. Thus, the flexibility of the stem would limit the force that can be transferred laterally by the entire dynein heavy chain to 0.6 pN at 8 nm displacement. This force is insufficient to support flagellar motility. So, if the stem were the only support for the globular head, then force would have to be transmitted linearly along the axis defined by the stem and B-link. Because this configuration is never observed, the hypothesis that dynein generates force by lateral displacement of the B-link is more attractive, but requires that the globular head of the dynein is stabilized by an additional means of support during the power stroke. We propose that the microtubule affinity of the tip of the B-link is independent of the ATP-dependent powerstroke, and that detachment from the B-subtubule is regulated by tension. A dynein cross-bridge cycle that incorporates an anchored head, together with a ratchet-like mechanism for microtubule translocation by the B-link, would have distinct advantages. This mechanism may reconcile dynein oscillation and interdoublet sliding within one cross-bridge mechanism.
Department of Biological Sciences, Oakland University, Rochester, Michigan 48309, USA. lindeman@oakland.edu
Charles B
CB
Lindemann
Alan J
AJ
Hunt
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002923:Cilia / Q000737:chemistry / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D005407:Flagella / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism*; D011487:Protein Conformation
D020409:Molecular Motor Proteins; D000255:Adenosine Triphosphate; D004398:Dyneins