title: Allosteric communication in the dynein motor domain.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Gira
authors.initials: G
authors.lastname: Bhabha
authors.affiliation: 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.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Cheng
authors.affiliation: Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Arne
authors.initials: A
authors.lastname: Moeller
authors.affiliation: Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Maofu
authors.initials: M
authors.lastname: Liao
authors.affiliation: National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Speir
authors.affiliation: Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000494:Allosteric Regulation; D002384:Catalysis; D018360:Crystallography, X-Ray; D004023:Dictyostelium / Q000737:chemistry; D004398:Dyneins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; C000596030:DYN1 protein, S cerevisiae; D004398:Dyneins