Cells need to be able to transport a variety of molecules, and even entire organelles, around a cell. Cells achieve this movement using molecular motors, which produce the force required for transport through the hydrolysis of ATP. The three major classes of biological motors are kinesins, myosins and dyneins, each of which plays vital roles in a huge variety of cellular processes. Molecular motors move their cargo along actin filaments (myosins) or microtubules (kinesins and dyneins), which act as highways within a cell for trafficking a wide variety of cargo. Kinesins (KIF proteins) are a family of molecular motors that contain a highly conserved ~340 residue motor domain that uses ATP hydrolysis to walk along a microtubule.
Kinesin I, or conventional kinesin (KIF5), was first identified as the motor behind the movement of particles along microtubules in the giant squid. However, it has since been found to drive the movement of several different types of cargo in many different types of cells. Kinesin I consists of a heterotetramer of two heavy chains (KHCs) and two light chains (KLCs). The KHC contains the catalytic motor domain (or head), followed by a short neck linker region that is important for guiding the direction of movement of cargo, and a coiled-coil dimerisation domain to which the KLC binds. KLCs bind cargo and regulate KHC motor activity. The two kinesin heads allow the molecule to ‘walk’ along the microtubule without detaching, which is important in order to prevent the kinesin-cargo complex from diffusing away from the microtubule. Kinesin motor activity is turned off in the absence of cargo by self-inhibition (tail folds back to prevent motor domain engaging with microtubules), so that cells are able to maintain concentrations of kinesin at a uniform level throughout the cell.
Many other proteins with kinesin-like motors have been identified, which together make up a kinesin superfamily that have been found in all eukaryotes, including fungi, invertebrates, animals and higher plants. The essential features of kinesin motor domains are their highly conserved nucleotide- and microtubule-binding motifs, which permit them to move their cargo along microtubules. Outside the motor domains, each kinesin-like protein has a unique sequence.
The direction in which cargo is transported is dependent in part upon the position of the motor domain, which can be located N-terminally (N-kinesins), C-terminally (C-kinesins) or internally (M-kinesins). In general, kinesins with N-terminal motor domains move their cargo towards the plus ends of microtubules located at the cell periphery, while kinesins with C-terminal motor domains move cargo towards the minus ends of microtubules located at the nucleus. In addition, interactions between kinesin and cargo-specific proteins may help steer the cargo towards a specific destination within the cell.