Kinesin heavy chain

Elluru, R., Bloom, G. S. and Brady, S. T. Fast axonal transport of kinesin in the rat visual system functionality of the kinesin heavy chain isoforms. Mol. Biol. Cell 6 21-40,1995. 

Kinesin heavy chains and kinesin-like proteins Dynamins and dynamin-like proteins... 

Mutations in motor proteins or IFs themselves (which may alter their associations with IFAPs or motors) lead to accumulations of IFs in ALS, Charcot-Marie Tooth disease 2, and Parkinson s (Goldstein and Yang, 2000 Helfand et al., 2004). Impaired assembly and transport of NFs is a critical determinant of neurodegenerative disease. Consistent with a critical role for kinesin in vivo, mice lacking the neuronal-specific conventional kinesin heavy chain KIF5A were shown to have accumulations of NF-H, as well as NF-M and NF-L, in the cell bodies of peripheral sensory neurons. The presence of these accumulations was accompanied by a reduction in... 

Fig. 1. Domain structures of typical members of the kinesin superfamily. (A) Bar diagram of the kinesin heavy chain (KHC) of conventional kinesin (kinesin-1 family) as a typical representative of N-type motors (motor domain at the N-terminus, red) the cartoon model beneath the bar diagram shows the tetrameric complex of two heavy and two light chains. (B) M-type kinesin like MCAK of the kinesin-13 family. (C) C-type kinesin like Ned of the kinesin-14 family.

Patel N, Thierry-Mieg D, Mancillas JR. 1993. Cloning by insertional mutagenesis of a cDNA encoding Caenorhabditis elegans kinesin heavy chain. Proc. Natl Acad. Sci. USA 90 9181-85... 

Kinesins mediate anterograde transport in a variety of organisms and tissues. Since its discovery, much has been learned about the biochemical, pharmacological and molecular properties of kinesin [44, 45], Kinesin is the most abundant member of the kinesin family in vertebrates and is widely distributed in neuronal and nonneuronal cells. The holoenzyme is a heterotetramer comprising two heavy chains (115-130 kDa) and two light... 

In neurons and non-neuronal cells, kinesin is associated with a variety of MBOs, ranging from synaptic vesicles to mitochondria to lysosomes. In addition to its role in fast axonal transport and related phenomena in non-neuronal cells, kinesin appears to be involved in constitutive cycling of membranes between the Golgi and endoplasmic reticulum. However, kinesin is not associated with all cellular membranes. For example, the nucleus, membranes of the Golgi complex and the plasma membrane all appear to lack kinesin. Kinesin interactions with membranes are thought to involve the light chains and carboxyl termini of heavy chains. However, neither this selectivity nor the molecular basis for binding of kinesin and other motors to membranes is well understood. 

The characteristic (consensus) sequence ofP-loops (the Walker A motif Walker et al., 1982) is Gly-x-x-x-x-Gly-Lys-Thr/Ser (the region in red in Fig. 5) this sequence is often used in bioinformatic searches to identify proteins related to this family. Each myosin and kinesin has a single P-loop. For example, Dictyostelium myosin II has the sequence as in Fig. 5 (179) G-E-S-G-A-G-K-T (186). On the other hand, dynein, with a heavy chain that partly forms a ringlike core complex of six AAA+ domains, has P-loop motifs in the first four of these domains (e.g., G-P-A-G-P-G-K-T). There may be a complex series of interactions between these various sites to generate movement, but the P-loop in the third domain has been shown to be essential for dynein motor function (Silvanovich et al., 2003). 

Stock, M. F., Guerrero, J., Cobb, B., Eggers, C. T., Huang, T. G., Li, X., and Hackney, D. D. (1999). Formation of the compact conformer of kinesin requires a COOH-terminal heavy chain domain and inhibits microtubule-stimulated ATPase activity. J. Biol. Chem. 274, 14617-14623. 

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. 

To date, approximately 10 different kinesin subfamilies have been identified. All contain a globular head (motor) domain, but they differ in their tail domains and several other properties. In most kinesins, the motor domain is at the N-termlnus (N-type) of the heavy chain but, in others, the motor domain is centrally located (M-type) or at the C-terminus (C-type). Both N- and M-type kinesins are (+) end-directed motors, whereas C-type kinesins are (—) end directed motors. Although most kinesins have two heavy chains (e.g., kinesin I), others have a single heavy chain (e.g.,... 

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