Structure and Functional Role of Dynein's Microtubule-Binding Domain

• Published in: Science (American Association for the Advancement of Science) Vol. 322; no. 5908; pp. 1691 - 1695
• Main Authors: Carter, Andrew P, Garbarino, Joan E, Wilson-Kubalek, Elizabeth M, Shipley, Wesley E, Cho, Carol, Milligan, Ronald A, Vale, Ronald D, Gibbons, I.R
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 12.12.2008; The American Association for the Advancement of Science
• Subjects: Adenosine triphosphatase; Adenosine triphosphatases; Adenosine Triphosphate - metabolism; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding and carrier proteins; Binding Sites; Biological and medical sciences; Biophysics; Cellular biology; Crystal structure; Crystallization; Crystallography, X-Ray; Crystals; Dimerization; Dimers; Dyneins - chemistry; Dyneins - metabolism; Freight; Fundamental and applied biological sciences. Psychology; Hydrophobic and Hydrophilic Interactions; Image Processing, Computer-Assisted; Mice; Microscopy, Electron; Microtubules; Microtubules - metabolism; Microtubules - ultrastructure; Modeling; Models, Molecular; Molecular biology; Molecular Sequence Data; Movement; Musical register; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Rodents; Rotation; Motility; Enzyme; Rodentia; Dynein ATPase; Structure function relationship; Vertebrata; Mammalia; Mouse; Cytoskeleton; Hydrolases; Microtubule; Molecular domain; Cytoplasm; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1164424

Dynein motors move various cargos along microtubules within the cytoplasm and power the beating of cilia and flagella. An unusual feature of dynein is that its microtubule-binding domain (MTBD) is separated from its ring-shaped AAA+ adenosine triphosphatase (ATPase) domain by a 15-nanometer coiled-coil stalk. We report the crystal structure of the mouse cytoplasmic dynein MTBD and a portion of the coiled coil, which supports a mechanism by which the ATPase domain and MTBD may communicate through a shift in the heptad registry of the coiled coil. Surprisingly, functional data suggest that the MTBD, and not the ATPase domain, is the main determinant of the direction of dynein motility.