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From Proteopedia

Kinesin

Kinesins are ATP dependent motor proteins that perform intracellular transport along microtubules. Kinesin is a very important protein in meiosis as well as mitosis allowing for the mitotic spindles to separate. The movement along microtubules is commonly known as anterograde transport.

Structure

The structure of Kinesin includes a motor domain which is involved in active transport. Since ATP is required for Kinesin to operate, the protein consists of an ATP-binding domain rich in alpha sheets and beta pleats. Most Kinesins have two motor domains that work simultaneously. Each motor domain is comprised of 350 amino acids, which fold into the alpha-beta secondary structure. The secondary structure includes central beta beta sheets that are surrounded by alpha helices, which supercoil into within the motor head to form the motor complex.

Kinesin also has 4 chains that include monomers, which dimerize to form the protein. The protein also consists of two head domains where ATP and microtubules will bind in order to initiate movement and or transport across the cell.

Some important amino acids that are included in this protein is glutamate, lysine, leucine, and isoleucine. lysine and glutamate residues extend from the loops of the protein to fix the orientation of the subunits in order to aid in binding to the ATP molecules. The polarity of lysine and glutamate also helps in stability and solubility. The hydrophobic side chain interactions within leucine and isoleucine tighten the dimerization of the protein.

Function

Kinesin is a very important structural protein. There are numerous functions that the motor protein Kinesin performs. Kinesin is extremely important in performing vesicle and intracellular transport for axons in the neuron cell. The movement of the axon essentially controls pre-synaptic and post-synaptic communication. In order for neurotransmitters to be successfully secreted into the synapse region, Kinesins must be present in order to aid in the movement of the axon and the formation of vesicles for the neurotransmitters. Once these vesicles are formed, these vesicles will be carried to the synaptic region by the Kinesin motor protein. Mutations in the motor domain of Kinesin can cause neurodegenerative disorders and paralysis.

Kinesins also play an important role in mitosis and meiosis. They have a role in assembling the spindles and separating the spindles during anaphase of mitosis and meiosis. The motor region of Kinesin is shown to produce tension for the spindles, which effectively separates the chromosomes in order to continue the cell cycle. Other Kinesin motors bind to the ends of chromosomes to ensure that the positioning of the chromosomes are correct at every stage. Mutations can subsequently cause female sterility and the abrupt stop of cell division. Cell division is a process that is part of microtubule dynamics, which is also controlled by Kinesin. These proteins are important in regulating the length and positioning of the mitotic spindles while promoting microtubule dynamics. Cytoskeletal transport and movement is also regulated through the aid of Kinesin.

Disease

Kinesin is an important protein that aids with axon transport and cell division. If there is a mutation of the gene and/or a defect of the protein, then there can be transport of pathogens or defective roles relating to neural impulses and cell division. Therefore, there are many different consequences of a faulty kinesis.

Defective role in cell division:

1. If kinesin cannot help regulate and aid cell division, then the cell can start dividing uncontrollably. Cancer cells take advantage of this to proliferate and grow rapidly.

2. This can pose a threat to the organism, but if kinesin is causing rapid cell division, then it can be used as an identifiable target and treated with drugs.

Defective role in axon transport:

1. A lot of environmental toxins can inactive kinesin and can no longer aid an axon in regards to transmitting neural signals. The motor functions of the human will start to deplete and will result in axonopathy (when nerves suddenly stop functioning).

2. Diffusion is inefficient for long-distance transport which is one reason why there are action potentials in he nervous system and kinesin helps the axon transport signals. But when long-distance transport is being inhibited, then the human's nervous system starts to be malfunction and people can start showing symptoms similar to mayotrophic lateral sclerosis (ALS).

References

Chevalier-Larsen, E., & Holzbaur, E. L. (2006). Axonal transport and degenerative disease. Biochimica et Biophysica Acta (BBA)- Molecular Basis of Disease, 1762(11-12), 1094-1108. Retrieved from https://www.sciencedirect.com/science/article/pii/S0925443906000731.

Endow, S. A., Kull, F. J., & Liu, H. (2010, October 15). Kinesins at a glance. Retrieved February 27, 2018, from http://jcs.biologists.org/content/123/20/3420

Rode, A. (n.d.). Dimeric Kinesin. Retrieved February 28, 2018, from https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch16_Rode_A_Kinesin_(Dimeric)-_-/Ch16_Rode_A_Kinesin_(Dimeric)_Kinesin.html