Cytoplasmic Dynein Moves Through Uncoordinated Stepping of the AAA+ Ring Domains

Cytoplasmic dynein is a homodimenc AAA+ motor that transports a multitude of cargos toward the microtubule minus end. How the two catalytic head domains interact and move relative to each other during processive movement is unclear. Here, we tracked the relative positions of both heads with nanomete...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2012-01, Vol.335 (6065), p.221-225
Main Authors: DeWitt, Mark A., Chang, Amy Y., Combs, Peter A., Yildiz, Ahmet
Format: Article
Language:English
Subjects:
Adenosine triphosphatases
Adenosine Triphosphate - metabolism
Biological and medical sciences
Cell structures and functions
Cytoplasm
Cytoplasm - metabolism
Cytoskeleton, cytoplasm. Intracellular movements
Dyneins - chemistry
Dyneins - metabolism
Fundamental and applied biological sciences. Psychology
Histograms
Hydrolysis
Kinetics
Lead
Microtubules
Microtubules - metabolism
Models, Biological
Models, Molecular
Molecular and cellular biology
Molecular biology
Motors
Protein Multimerization
Protein Structure, Tertiary
Proteins
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - metabolism
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Summary:Cytoplasmic dynein is a homodimenc AAA+ motor that transports a multitude of cargos toward the microtubule minus end. How the two catalytic head domains interact and move relative to each other during processive movement is unclear. Here, we tracked the relative positions of both heads with nanometer precision and directly observed the heads moving independently along the microtubule. The heads remained widely separated, and their stepping behavior varied as a function of interhead separation. One active head was sufficient for processive movement, and an active head could drag an inactive partner head forward. Thus, dynein moves processively without interhead coordination, a mechanism fundamentally distinct from the hand-over-hand stepping of kinesin and myosin.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1215804