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Kinesins are a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule cables powered by the hydrolysis of ATP (thus kinesins are ATPases). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cargo such as axonal transport.



Members of the kinesin family vary in shape but the typical kinesin is a protein dimer (molecule pair) consisting of two heavy chains and two light chains. The heavy chain comprises a globular head (the motor domain) connected via a short, flexible neck linker to the stalk - a long, central coiled-coil region - that ends in a tail region formed with a light-chain. The stalks intertwine to form the kinesin dimer. Cargo binds to the tail while each head has two separate binding sites: one for the microtubule and the other for ATP. ATP binding and hydrolysis as well as ADP release change the conformation of the microtubule-binding domains and the orientation of the neck with respect to the head; this results in the motion of the kinesin. Several structural elements in the head, including a central beta-sheet domain and the Switch I and II domains, have been implicated as mediating the interactions between the two binding sites and the neck domain. Kinesins are related structurally to G proteins, which are also ATPases; several structural elements are shared between the two families, notably the Switch I and Switch II domains.

Cargo transport

In the cell, small molecules such as gases and glucose diffuse to where they are needed. Large molecules synthesised in the cell body, intracellular components such as vesicles, and organelles such as mitochondria are too large (and the cytosol too crowded) to diffuse to their destinations. Motor proteins fulfill the role of transporting large cargo about the cell to their required destinations. Kinesins are motor proteins that transport such cargo by walking unidirectionally along microtubule tracks hydrolysing one molecule of adenosine triphosphate (ATP) at each step.[1] It was thought that ATP hydrolysis powered the kinesin walk[2] but it now seems that diffusion and the force of binding to the microtubule is what pulls the cargo along while the binding of ATP assists the direction of motion.[3]

Direction of motion

Motor proteins travel in a specific direction along a microtubule. This is because the microtubule is polar, the heads only bind to the microtubule in one orientation, and ATP hydrolysis drives the molecule in one direction.

Most kinesins walk towards the positive end of a microtubule which, in most cells, entails transporting cargo from the centre of the cell towards the periphery. This form of transport is known as anterograde transport.

Some kinesins {EG5}, and a different type of motor protein known as dyneins, move towards the minus end of the microtubule. Thus they transport cargo from the periphery of the cell towards the centre. This is known as retrograde transport. However, dyneins are the much faster and more ubiquitous of the microtubule-binding retrograde transporters.

Proposed mechanisms of movement

Kinesin accomplishes transport by "walking" along a microtubule. Two mechanisms have been proposed to account for this movement.

  • In the "hand-over-hand" mechanism, the kinesin heads step past one another, alternating the lead position.
  • In the "inchworm" mechanism, one kinesin head always leads, moving forward a step before the trailing head catches up.

Despite some remaining controversy, mounting experimental evidence points towards the hand-over-hand mechanism as being more likely.[4] The movement is not unlike the way we walk when toeing a line.[5]

Kinesin and mitosis

In recent years, it has been found that microtubule-based molecular motors (including a number of kinesins) have a role in mitosis (cell division). The mechanism by which the cytoskeleton of the daughter cell separates from that of the mother cell was unclear. It seems that motors organize the two separate microtubule asters into a metastable structure independent of any external positional cues. This self-organization is in turn dependent on the directionality of the motors as well as their processivity (ability to walk). Thus motors are necessary for the formation of the mitotic spindle assemblies that perform chromosome separation. Specifically, proteins from the Kinesin 13 family act as regulators of microtubule dynamics. The prototypical member of this family is MCAK (formerly Kif2C, XKCM1, Gene KIF2C) which acts at the ends of microtubule polymers to depolymerize them. The function of MCAK in cells and its mechanism in vitro is currently being investigated by numerous labs.

Additional images

See also


  1. ^ Schnitzer MJ, Block SM (1997). "Kinesin hydrolyses one ATP per 8-nm step". Nature 388: 386–390. PMID 9237757.
  2. ^ Rice S, Lin AW, Safer D, Hart CL, Naber N, Carragher BO, Cain SM, Pechatnikova E, Wilson-Kubalek EM, Whittaker M, Pate E, Cooke R, Taylor EW, Milligan RA, Vale RD (1999). "A structural change in the kinesin motor protein that drives motility". Nature 402: 778-784.
  3. ^ Mather WH, Fox RF (2006). "Kinesin's Biased Stepping Mechanism: Amplification of Neck Linker Zippering". Biophysical Journal 91: 2416-2426.
  4. ^ Yildiz A, Tomishige M, Vale RD, Selvin PR (2004). "Kinesin Walks Hand-Over-Hand". Science 303: 676-8. PMID 14684828.
  5. ^ Asbury CL (2005). "Kinesin: world’s tiniest biped". Current Opinion in Cell Biology 17: 89-97. PMID 15661524.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Kinesin". A list of authors is available in Wikipedia.
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