Max-Planck Unit for
Structural Molecular Biology Hamburg

 Mandelkow lab  

KTdock

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KTdock
 

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Microtubule protofilament with the bound motor domain of Neurospora crassa conventional kinesin. Model based on Song et al. (2001). In the microtubule, two alpha-tubulin subunits (alphaT1 and alphaT2) and a beta-tubulin (betaT1) are shown (structure adapted from Lowe et al., 2001). Kinesin would move along the microtubule towards the top of the figure. N. crassa kinesin and the microtubule interact predominantly through helices H11 and H12 (yellow coils) and the carboxy-terminal tail (thin red strand, C) of betaT1, and the region of kinesin that includes the structural elements in dark blue (alpha4-L12-alpha5 and beta5a-L8). Other interactions may include the carboxy-terminal tail (pink, C) of alphaT2 and kinesin’s neck linker/neck region (grey), as well as alphaT1 and kinesin’s L11. The top of the kinesin core shows the neck domain in two conformations: a random coil found in NcKin (protein backbone in grey), and the ordered conformation of alpha7 from rat brain kinesin (RnKin; Sack et al. 1997) in red. The group of yellow spheres represents GTP and GDP in tubulin and ADP in NcKin. The drug taxol (red spheres) is shown bound to betaT1.

> Song, Y.H., Marx, A., Muller, J., Woehlke, G., Schliwa, M., Krebs, A., Hoenger, A. and Mandelkow, E. (2001) Structure of a fast kinesin: implications for ATPase mechanism and interactions with microtubules. Embo J, 20, 6213-6225.
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> Lowe, J., Li, H., Downing, K.H. and Nogales, E. (2001) Refined Structure of alphabeta-Tubulin at 3.5 A Resolution. J Mol Biol, 313, 1045-1057.
> Sack, S., Müller, J., Marx, A., Thormählen, M., Mandelkow, E.M., Brady, S.T. and Mandelkow, E. (1997) X-ray structure of motor and neck domains from rat brain kinesin. Biochemistry, 36, 16155-16165.
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Kinwalk

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Model of kinesin dimer walking along a microtubule protofilament. (Hoenger et al.2000). The kinesin dimer is shown with two motor domains and the alpha-helical neck forming a coiled-coil; the remainder of the stalk is not visible (for crystal structures see Sack et al., 1997; Kozielski et al., 1997). The tubulin protofilament is adapted from Nogales et al. (1999). alpha-Tubulin is pale blue, beta-Tubulin is pale green. Kinesin walks towards the plus-end of microtubules (right side of picture). The motor domains attach to successive beta-Tubulin subunits spaced 8 nm apart, and each head advances 16 nm at a time. The two heads must move in a non-equivalent fashion in order to avoid twisting the stalk. The upper (C-terminal) part of the coiled-coil neck is shown to be permanently connected since it has a high coiled-coil potential, similar to a leucine zipper. The lower part of the neck is shown to open and close reversibly in order to allow the heads to detach, move, and reattach. This is coupled to a reorientation of the linker region (yellow) between the neck helix and the motor domain. For reviews and additional models see Vale & Milligan (2000).

> Hoenger, A., Thormählen, M., Diaz-Avalos, R., Doerhoefer, M., Goldie, K.N., Müller, J. and Mandelkow, E. (2000) A new look at the microtubule binding patterns of dimeric kinesins. J Mol Biol, 297, 1087-103.
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> Vale, R.D. and Milligan, R.A. (2000) The way things move: looking under the hood of molecular motor proteins. Science, 288, 88-95.

 

Neurospora crassa kinesin (NcKin)

 

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Kar3

 

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Surface representation of the nucleotide binding pockets of NcKin and Kar3 with bound ADP. The surface is colored according to the surface potential, blue positive, red negative.Coordinates of NcKin from Gulick et al. (1998), PDB code 3KAR.

> Gulick, A.M., Song, H., Endow, S.A. and Rayment, I. (1998) X-ray crystal structure of the yeast Kar3 motor domain complexed with Mg.ADP to 2.3 A resolution. Biochemistry, 37, 1769-1776.

 

NMR structure

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Kinesin dimer with multiple neck - hinge conformations. Conformations of the neck - hinge region determined by nmr methods (Seeberger et al., 2000) superimposed on the x-ray structure of dimeric rat kinesin motor domain RnKin379 (Kozielski et al., 1997).

> Seeberger, C., Mandelkow, E. and Meyer, B. (2000) Conformational Preferences of a Synthetic 30mer Peptide from the Interface between the Neck and Stalk Regions of Kinesin. Biochemistry, 39, 12558-12567.
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> Kozielski, F., Sack, S., Marx, A., Thormählen, M., Schönbrunn, E., Biou, V., Thompson, A., Mandelkow, E.M. and Mandelkow, E. (1997) The crystal structure of dimeric kinesin and implications for microtubule-dependend motility. Cell, 91, 985-994.
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