Allosteric communication in the Dynein motor domain

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  • Gira Bhabha, Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA., Ukendt
  • Hui-Chun Cheng, Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: hccheng@life.nthu.edu.tw., Ukendt
  • Nan Zhang, Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA., Ukendt
  • Arne Moeller
  • Maofu Liao, Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Ukendt
  • Jeffrey A Speir, National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Ukendt
  • Yifan Cheng, Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Ukendt
  • Ronald D Vale, Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: ron.vale@ucsf.edu., Ukendt

Dyneins power microtubule motility using ring-shaped, AAA-containing motor domains. Here, we report X-ray and electron microscopy (EM) structures of yeast dynein bound to different ATP analogs, which collectively provide insight into the roles of dynein's two major ATPase sites, AAA1 and AAA3, in the conformational change mechanism. ATP binding to AAA1 triggers a cascade of conformational changes that propagate to all six AAA domains and cause a large movement of the "linker," dynein's mechanical element. In contrast to the role of AAA1 in driving motility, nucleotide transitions in AAA3 gate the transmission of conformational changes between AAA1 and the linker, suggesting that AAA3 acts as a regulatory switch. Further structural and mutational studies also uncover a role for the linker in regulating the catalytic cycle of AAA1. Together, these results reveal how dynein's two major ATP-binding sites initiate and modulate conformational changes in the motor domain during motility.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind159
Nummer4
Sider (fra-til)857-68
Antal sider12
ISSN0092-8674
DOI
StatusUdgivet - 6 nov. 2014

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