Kinesin family analysis

Kinesins constitute a large superfamily of motor proteins in eukaryotic cells. They perform diverse tasks such as vesicle and organelle transport and chromosomal segregation in a microtubule- and ATP-dependent manner. In recent years, the genomes of a number of eukaryotic organisms have been completely sequenced. Subsequent studies revealed and classified the full set of members of the kinesin superfamily expressed by these organisms.
The first kinesin was isolated from squid giant axons as a protein responsible for fast axonal transport [1, 2]. This conventional kinesin (KHC) was shown to be a tetramer including two heavy and two light chains. The heavy chain consists of an N-terminal motor domain with microtubule affinity and ATPase activity followed by an extended coiled-coil region containing the light chain binding site [3] and a C-terminal domain that binds to the cargos. Like KHC, most kinesins have their motor domains at the N-terminus. However, in some kinesins, the motor domain is located in the centre of the molecule and a few others have C-terminal motor domains. In general, the position of the motor domain determines the directionality of transport: N-terminal kinesins move to the plus end and C-terminal kinesins to the minus end of microtubules [4]. Kinesins with central motor domains do not generate movement but function as microtubule depolymerases [5].

Our interest is to understand how kinesin works at atomic resolution, as well as how the kinesin mediated transport is organised at a cellular scale. One of the first questions we want to answer is how many kinesins a cell needs to survive. Therefore, we are in the process of identifying all kinesins in all sequenced eukaryotic genomes. In a first step, we reported the identification of thirteen kinesin genes exploiting the information from the raw shotgun reads of the Dictyostelium discoideum genome project [6] (Figure 1). A phylogenetic tree of 390 kinesin motor domain sequences was built, grouping the Dictyostelium kinesins into nine subfamilies (Figure 2). According to known cellular functions or strong homologies to kinesins of other organisms, four of the Dictyostelium kinesins are involved in organelle transport, six are implicated in cell division processes, two are predicted to perform multiple functions, and one kinesin may be the founder of a new subclass.

Dicty kinesins Dicty kinesins
Figure 1

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Figure 2

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[1]RD Vale, TS Reese, MP Sheetz: Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 1985, 42:39-50.
[2]ST Brady: A novel brain ATPase with properties expected for the fast axonal transport motor. Nature 1985, 317:73-5.
[3]RJ Diefenbach, JP Mackay, PJ Armati, AL Cunningham: The C-terminal region of the stalk domain of ubiquitous human kinesin heavy chain contains the binding site for kinesin light chain. Biochemistry 1998, 37:16663-70.
[4]SA Endow: Determinants of molecular motor directionality. Nat Cell Biol 1999, 1:E163-7.
[5]Y Ovechkina, L Wordeman: Unconventional motoring: an overview of the kin C and kin I kinesins. Traffic 2003, 4:367-75.
[6]M Kollmar, G Glöckner: Identification and phylogenetic characterisation of Dictyostelium discoideum kinesin proteins. BMC Genomics 2003, 4:47.
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MPG
MPI for biophysical chemistry
Uni-Goettingen