Dynein heavy chain

Asai, D.J. Brokaw, C.J. (1993). Dynein heavy chain isoforms and axonemal motility. Trends Cell Biol. 3. 398-402. 

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. 

Mocz, G., and Gibbons, I. R. (2001). Model for the motor component of dynein heavy chain based on homology to the AAA family of oligomeric ATPases. Structure (Camb.) 9, 93-103. 

Chen, X. J., Levedakou, E. N., Millen, K. J., Wollmann, Ik. L., Soliven, B. and Popko, B. (2007) Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J Neurosci 27, 14515-14524. 

Comparison of the amino acid sequences of myosins, kinesins, and dyneins did not reveal significant relationships between these protein families but, after their three-dimensional structures were determined, members of the myosin and kinesin families were found to have remarkable similarities. In particular, both myosin and kinesin contain P-loop NTPase cores homologous to those found in G proteins. Sequence analysis of the dynein heavy chain reveals it to be a member of the AAA subfamily of P-loop NTPases that we encountered previously in the context of the 19S proteasome (Section 23.2.21. Dynein has six sequences encoding such P-loop NTPase domains arrayed along its length. Thus, we can draw on our knowledge of G proteins and other P-loop NTPases as we analyze the mechanisms of action of these motor proteins. 

D. J. Asai and M.P. Koonce. 2001. The dynein heavy chain Structure, mechanics and evolution Trends Cell Biol. 11 196-202. (PubMedl... 

Inaba, K. (1995) Atp-dependent conformational changes of dynein—Evidence for changes in the interaction of dynein heavy-chain with the intermediate chain-1, J. Biochem. Tokyo 117, 903-907. 

One striking difference that dynein exhibits compared to kinesins and myosins is that dynein has AAA (ATPases Associated with a variety of cellular Activities) modules [ 77-79], which indicate that its mode of working will be entirely different from kinesins and myosins. This puts dyneins into the AAA superfamily of mechanoenzymes. The dynein heavy chains contain six tandemly linked AAA modules [80,81] with the head having a ring-like domain organization, typical of AAA superfamily. Four of these are nucleotide binding motifs, named P1-P4, but only PI (AAAI) is able to hydrolyze ATP. 

Koonce M.P. 1997. Identification of a microtubule-binding domain in a cytoplasmic dynein heavy chain. / Biol Chem. 272 19714-19718. 

Ibanez-Tallon, 1., Pagenstecher, A., Fliegauf, M., Olbrich, H., Kispert, A., Ketelsen, U.-P., North, A., Heintz, N., and Omran, H. (2004) Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum. Mol Genet., 13, 2133-2141. 

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