Kinesin 13

The Kinesin 13 Family are a subfamily of the molecular motor proteins known as kinesins. Most kinesins transport materials or cargo around the cell while traversing along microtubule polymer tracks with the help of ATP-hydrolysis-created energy. They are easily identified by their three typical structural components including a highly conserved structural domain, catalytic core, and microtubule binding sites. The kinesin 13 family, unlike other kinesins, has an internally positioned motor domain. They were initially named KIF-M because of the unique location of their catalytic core in the middle of the polypeptide between the N-terminal globular domain and the C-terminal stalk but they are truly special due to their versatile nature. The Kinesin 13 family's molecular mechanism is less understood than other classes of kinesins which have their motor domains at one end of the molecule or the other. They are capable of traveling to both the minus and plus ends of microtubules whereas most motors are unidirectional. Thus they can catalytically depolymerize a microtubule from both ends making it a very efficient process.

The prototypical member of the Kinesin 13 family is MCAK (mitotic centromere associated kinesin). Formerly known as Kif2C or KCM1 this molecule has been shown to be essential to mitosis. Other members of this class include Kif2A, Kif2B, and Kif24.

The exact mechanism of Kinesin 13 activated microtubule depolymerization remains unclear, however, recent biochemical and structural studies revealed some more detailed class specific features enabling researchers to formulate the following model. (Refer to Figure 6 in referenced Ogawa article for illustrated description.) The protein first contacts the side wall of a microtubule. This is not a stable interaction because the convex surface of the catalytic core does not fit to the flat surface of the straight microtubule protofilament. Steric hindrance between the molecule neck and adjacent protofilament further inhibits full contact between protein and the microtubule and only facilitates one-dimensional diffusion along the microtubule. At this time, The protein's nucleotide binding pocket is trapped in an open state so that the structure is not hydrolyzing ATP. Once the motor reaches the end of the microtubule, the protofilament spontaneously curves itself allowing motor to make full contact with the tubulin subunit. More MCAK molecules collectively bind to the curved region supporting the theory that they do not actively peel away the microtubule but they wait patiently for it to adopt this curved conformation. They stabilize the curved conformation by binding to the end of the microtubule and then catalyze depolymerization.

References

Ogawa, T., Nitta, R., Okada, Y., and N. Hirokawa (2004) Cell 116: 591-602. [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSN-4BSKPFC-D&_user=423519&_coverDate=02%2F20%2F2004&_fmt=full&_orig=search&_qd=1&_cdi=7051&view=c&_acct=C000020258&_version=1&_urlVersion=0&_userid=423519&md5=e9bbf4940109f931dc67ed73439122cb&ref=full A Common Mechanism for Microtubule Destabilizers—M Type Kinesins Stabilize Curling of the Protofilament Using the Class-Specific Neck and Loops]

External links

* [http://download.cell.com/supplementarydata/cell/116/4/591/DC1/index.htm Video Illustrations]