TY - JOUR
T1 - Structural mechanism of the dynein power stroke
AU - Lin, Jianfeng
AU - Okada, Kyoko
AU - Raytchev, Milen
AU - Smith, Maria C.
AU - Nicastro, Daniela
N1 - Funding Information:
We thank D. T. N. Chen (Brandeis University) for providing Strongylocentrotus purpuratus sperm; M. Porter (University of Minnesota) for providing the pseudo wild-type Chlamydomonas strain; and C. Xu for providing training and management of the Brandeis EM facility. We are grateful to D. Mitchell (SUNY Upstate Medical University), and J. Gelles, D. DeRosier and T. Heuser (all from Brandeis University) for critically reading the manuscript. This work was supported by financial support from the National Institutes of Health (GM083122 to D.N.).
PY - 2014
Y1 - 2014
N2 - Dyneins are large microtubule motor proteins required for mitosis, intracellular transport and ciliary and flagellar motility. They generate force through a power-stroke mechanism, which is an ATP-consuming cycle of pre-and post-power-stroke conformational changes that cause relative motion between different dynein domains. However, key structural details of dynein's force generation remain elusive. Here, using cryo-electron tomography of intact, active (that is, beating), rapidly frozen sea urchin sperm flagella, we determined the in situ three-dimensional structures of all domains of both pre-and post-power-stroke dynein, including the previously unresolved linker and stalk of pre-power-stroke dynein. Our results reveal that the rotation of the head relative to the linker is the key action in dynein movement, and that there are at least two distinct pre-power-stroke conformations: pre-I (microtubule-detached) and pre-II (microtubule-bound). We provide three-dimensional reconstructions of native dyneins in three conformational states, in situ, allowing us to propose a molecular model of the structural cycle underlying dynein movement.
AB - Dyneins are large microtubule motor proteins required for mitosis, intracellular transport and ciliary and flagellar motility. They generate force through a power-stroke mechanism, which is an ATP-consuming cycle of pre-and post-power-stroke conformational changes that cause relative motion between different dynein domains. However, key structural details of dynein's force generation remain elusive. Here, using cryo-electron tomography of intact, active (that is, beating), rapidly frozen sea urchin sperm flagella, we determined the in situ three-dimensional structures of all domains of both pre-and post-power-stroke dynein, including the previously unresolved linker and stalk of pre-power-stroke dynein. Our results reveal that the rotation of the head relative to the linker is the key action in dynein movement, and that there are at least two distinct pre-power-stroke conformations: pre-I (microtubule-detached) and pre-II (microtubule-bound). We provide three-dimensional reconstructions of native dyneins in three conformational states, in situ, allowing us to propose a molecular model of the structural cycle underlying dynein movement.
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U2 - 10.1038/ncb2939
DO - 10.1038/ncb2939
M3 - Article
C2 - 24727830
AN - SCOPUS:84899988126
SN - 1465-7392
VL - 16
SP - 479
EP - 485
JO - Nature cell biology
JF - Nature cell biology
IS - 5
ER -