Microtubules dynein binding

Although dynein binding to MTs is not stabilized by AMP-PNP, both cytoplasmic dynein and kinesin associate with microtubules in nucleotide-depleted extracts and both are released by addition of ATP. Early studies with... 

ATP hydrolysis is activated by dynein binding to microtubule, in accordance with the experimental observation that the presence of microtubule stimulates the ATPase activity of dynein [64]. The rates of other chemical transitions (binding of ATP and release of ADP Pj) depend explicitly only on a, so that the chemical reaction is not tightly coupled to the translocation of dynein. The transitions between chemical states are random processes and the probabilities for the occurrence of these transitions are determined by the rate constants of the transitions. 

The minima of such a potential is located at where is a force constant, x is the position of the center of mass of dynein, Xj is the coordinate of the dynein binding sites along microtubule, and is the maximum step length (30 nm) that a dynein can achieve. 

Motor proteins move along microtubules or F-actin. The respective motor domains are linked to their cargoes via adaptor proteins. Kinesin motors move only to the plus and dynein motors only to the minus ends of microtubules. Myosin motors move along F-actin. When motors are immobilized at their cargo binding area, they can move microtubules or F-actin, respectively. 

Both dynein and MAP2 interact with microtubules at the same binding sites, namely, the C termini of a- and p-tubulin. Also, MAP2 inhibits the microtubule-activated ATPase of dynein and prevents microtubule gliding on dynein-coated glass coverslips. Thus, MAP2 and other fibrous MAPs may be regulators of microtubule-based motility in vivo (Paschal et al., 1989). 

Even though dynein, kinesin, and myosin serve similar ATPase-dependent chemomechanical functions and have structural similarities, they do not appear to be related to each other in molecular terms. Their similarity lies in the overall shape of the molecule, which is composed of a pair of globular heads that bind microtubules and a fan-shaped tail piece (not present in myosin) that is suspected to carry the attachment site for membranous vesicles and other cytoplasmic components transported by MT. The cytoplasmic and axonemal dyneins are similar in structure (Hirokawa et al., 1989 Holzbaur and Vallee, 1994). Current studies on mutant phenotypes are likely to lead to a better understanding of the cellular roles of molecular motor proteins and their mechanisms of action (Endow and Titus, 1992). 

Silvanovich, A., Li, M-G., Serr, M., Mische, S., and Hays, T. S. (2003). The third P-loop domain in cytoplasmic dynein heavy chain is essential for dynein motor function and ATP-sensitive microtubule binding. Mol. Biol. Cell 14, 1355-1365. 

Microtubules are hollow cylinders about 23 nm in diameter, most commonly comprising 13 protofilaments, which in turn are polymers of a- and /3-tubulin. They have a very dynamic behaviour, binding GTP for polymerisation. They are commonly organised by the centrosome. In nine triplet sets (star-shaped), they form the centrioles, and in nine doublets oriented about two additional microtubules (wheel-shaped) they form cilia and flagella. The latter formation is commonly referred to as a 9-1-2 arrangement, wherein each doublet is connected to another by the protein dynein. Microtubules play key roles in ... 

PPIases are also associated with motor proteins the first PPIase domain of hFKBP52 (and to a lesser extent hCyp40) binds to the microtubule-associated motor protein dynein [21] and some authors propose that the amino acyl proline CTI plays an important part in the protein transconformation that directs relative molecular motion in contractile muscle fibers [22]. However, there is presently no evidence that PPIases are directly implicated in muscle diseases. 

Dyneins (20) ATP Multiple heavy, intermediate, and light chains head domains with ATPase activity and microtubule-binding site Cytoplasm Transport of cargo vesicles beating of cilia and eukaryotic flagella... 

FIGURE 3-23 Motor protein-dependent movement of cargo. The head domains of myosin, dynein, and kinesin motor proteins bind to a cytoskeletal fiber (microfilaments or microtubules), and the tail domain attaches to one of various types of cargo—in this case, a membrane-limited vesicle. Hydrolysis of ATP in the head domain causes the head domain to "walk" along the track in one direction by a repeating cycle of conformational changes. 

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