Kinesin 5 is a molecular motor protein found within eukaryotic cells. These proteins convert chemical energy, primarily from ATP, into mechanical force. Kinesin 5 functions as a cellular transporter and organizer, moving components to their correct locations and contributing to the cell’s internal architecture. This movement occurs along specialized cellular tracks known as microtubules, which serve as pathways for intracellular cargo.
The Mitotic Motor
Kinesin 5, also identified as Eg5 or KIF11, plays a unique role during cell division, known as mitosis. This protein is characterized by its homotetrameric structure, often described as a dimer-of-dimers, where four identical subunits are arranged to form a bipolar complex. This arrangement allows Kinesin 5 to simultaneously bind to and cross-link two anti-parallel microtubules within the developing mitotic spindle.
By actively sliding these microtubules past each other, Kinesin 5 generates outwardly-directed forces that are necessary for the separation of spindle poles, which house the duplicated centrosomes. This pushing action is fundamental for the proper formation and maintenance of the bipolar mitotic spindle, the cellular machinery that ensures chromosomes are accurately segregated into new daughter cells.
Kinesin 5 participates in the self-assembly of this spindle structure and contributes to microtubule flux. Without Kinesin 5, cells often fail to establish a bipolar spindle, instead forming an abnormal monopolar spindle, leading to a breakdown in cell division and failure of mitosis.
How Kinesin 5 Moves
Kinesin 5 moves along its microtubule tracks, powered by the hydrolysis of adenosine triphosphate (ATP), the cell’s energy currency. Kinesin 5 has two motor domains, or “heads,” at each end of its elongated structure, interacting directly with microtubules. ATP hydrolysis fuels conformational changes in these motor domains and the flexible neck linker.
This enables a coordinated “stepping” motion: one motor domain remains attached while the other detaches, swings forward, and reattaches further along the microtubule. This processive movement typically propels the protein towards the microtubule’s plus end, advancing about 8 nanometers per step.
Its central stalk and C-terminal tail domains orient the motor subunits, enhance microtubule affinity, and contribute to crosslinking and force production. This regulated mechanism ensures efficient cellular transport.
Kinesin 5 and Cell Health
Dysfunction in Kinesin 5 activity carries implications for cell health. When this motor protein does not operate correctly, it can lead to errors during cell division, specifically resulting in the missegregation of chromosomes. This means that daughter cells may receive an unequal number of chromosomes, a condition known as aneuploidy.
Persistent instances of chromosome missegregation contribute to chromosomal instability (CIN), a state characterized by ongoing changes in the cell’s chromosome set over multiple divisions. Such genomic instability is a known factor in the development and progression of various diseases, particularly cancer.
While some level of CIN can provide a selective advantage to cancer cells, excessively high rates can be detrimental, often leading to cell death. Tumor cells may adapt to moderate CIN through mechanisms such as the loss of the p53 tumor suppressor pathway, which normally limits the proliferation of aneuploid cells.
Targeting Kinesin 5
The distinct role of Kinesin 5 in cell division makes it an appealing target for therapeutic strategies, particularly in cancer treatment. Cancer cells are characterized by uncontrolled, rapid proliferation.
Inhibitors designed to target Kinesin 5, known as mitotic inhibitors, disrupt its ability to form and maintain the mitotic spindle. These drugs often act as allosteric inhibitors, binding to a unique site on the protein to alter its function.
By interfering with this process, these inhibitors induce mitotic arrest in cancer cells, ultimately triggering programmed cell death. This strategy offers selective targeting of rapidly dividing cells. Early inhibitors have led to newer, more potent compounds, some of which have advanced into clinical trials.