M Type Kinesins

M Type Kinesins (KIF-M) are a subfamily of the molecular motor proteins known as kinesins. Simply stated, their task is to 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. Composed of only one class, KIF2, the KIF-M family is less understood than KIF-Ns (with their catalytic core at the N-terminus) or KIF-Cs (with their catalytic core at the C-terminus). 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. 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 exact mechanism of KIF-M 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.) KIF-M 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 KIF-M neck and adjacent protofilament further inhibits full contact between KIF-M and the microtubule and only facilitates one-dimensional diffusion along the microtubule. At this time, KIF-M'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 KIF-M to make full contact with the tubulin subunit. More KIF-M 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.