Kinesins motor domain binding

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. 

Motor proteins move along MTs in an ATP-dependent manner. Members of the superfamily of kinesin motors move only to the plus ends and dynein motors only to the minus ends. The respective motor domains are linked via adaptor proteins to their cargoes. The binding activity of the motors to MTs is regulated by kinases and phosphatases. When motors are immobilized at their cargo-binding area, they can move MTs. 

Examining these structures and the fact that they are all powered by ATP, the question remains as to how force is actually produced. Geeves and Holmes (2005) argue that myosin acts by the specific coupling between different myosin head states and different positions of the lever arm on the motor domain, so that, once attached to actin, the myosin acts as an ATP-driven motor where the energy released by ATP hydrolysis is direcdy coupled to the performance of mechanical work. However, Marx et al. (2005) argue that in some cases the kinesins appear to act as thermal ratchets. In this case, the attachment of a second head, once the first head has bound, is an event controlled by thermal motion, but, presumably for steric reasons, the head is more likely to bind to the microtubule in the... 

Kinesin-1 comprises three major domains the N-terminal motor domain that can be subdivided into the core motor domain and the adjacent neck linker and neck region, the central stalk domain, and the C-terminal tail or light chain-binding domain (Fig. 1A). The core motor domain has a length of about 325 amino acids and contains both the microtubule and the nucleotide binding elements. In different kinesin families, this motor... 

Structures of the motor domains of three different kinesin-14 proteins, kinesins with a C-terminal motor domain, have been determined so far (1) the Drosophila nonclaret disjunctional gene product (DmNcd), (2) the yeast kinesin-like nuclear fusion protein (ScKar3), and (3) the kinesin-like calmodulin binding protein from potato (PoKCBP). 

Forkhead-associated domains (FHA domains) were originally identified as conserved sequence elements within a subset of forkhead transcription factors and were subsequently found, e. g., in other transcription factors, in protein kinases, protein phosphatases, and kinesin motors (review Durocher and Jackson, 2002). FHA domains comprise up to 140 amino acids, exhibit binding specificity toward phosphothreonine residues, and efficiently discriminate against phosphoserine residues. 

A puzzling discovery was that the motor domain of kinesin, which binds primarily to the P subunits of tubulin (Fig. 7-34) and moves toward the fast growing plus end of the microtubule, is located at the N terminus of the kinesin molecule, just as is myosin. However, the Ned and Kar3 motor domains are at the C-terminal ends of their peptide chains and move their "cargos" toward the minus ends of microtubules. Nevertheless, the structures of all the kinesin heads are conserved as are the basic chemical mechanisms. The differences in directional preference are determined by a short length of peptide chain between the motor domain and the neck, which allows quite different geometric arrangements when bound to microtubules. Like Ned, myosin VI motor domains also move "backwards" toward the pointed (minus) ends of actin filaments. " ... 

---