Kinesin 609808 223907365 2008-07-06T13:14:47Z ToNToNi 5531086 [[ca:Cinesina]] [[Image:Kinesin cartoon.png|thumb|The kinesin dimer attaches to, and moves along, microtubules.]] [[Image:Kinesin.png|thumb|Kinesins (the one shown is from PDB code 3kin) and dyneins walk along microtubules dragging their ''cargo'' along with them (red: ATP) (bottom: domain that links to the cargos) ([http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb64_1.html more details...])]] '''Kinesins''' are a class of [[motor protein]]s found in [[eukaryotic]] cells. Kinesins move along [[microtubule]] cables powered by the [[hydrolysis]] of [[Adenosine triphosphate|ATP]] (thus kinesins are [[ATPase]]s). The active movement of kinesins supports several cellular functions including [[mitosis]], [[meiosis]] and transport of cargo such as [[axonal transport]]. ==Structure== 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 site]]s: 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 hydrolyze [[GTP]] instead of ATP. 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]] [[Brownian motion|diffuse]] to where they are needed. Large molecules synthesised in the cell body, intracellular components such as [[vesicle (biology)|vesicle]]s, 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<ref name="Schnitzer">{{cite journal|author= Schnitzer MJ, Block SM | title = Kinesin hydrolyses one ATP per 8-nm step | journal = Nature | date = 1997 | volume = 388 | pages = 386–390 | pmid = 9237757|doi= 10.1038/41111}}</ref>. It was thought that ATP [[hydrolysis]] powered each step, the energy released propelling the head forwards to the next binding site<ref>{{cite journal|author= Vale RD, Milligan RA | title = The way things move: looking under the hood of molecular motor proteins | journal = Science | date = 2000 | volume = 288(5463) | pages = 88–95}}</ref>. It now seems that the head diffuses forward and the force of binding to the microtubule is what pulls the cargo along<ref name="Mather">{{cite journal|author= Mather WH, Fox RF | title = Kinesin's Biased Stepping Mechanism: Amplification of Neck Linker Zippering | journal = Biophysical Journal | date = 2006 | volume = 91 | pages = 2416–2426|doi= 10.1529/biophysj.106.087049 | pmid = 16844749}}</ref>. ==Direction of motion== Motor proteins travel in a specific direction along a microtubule. This is because the microtubule is polar and the heads only bind to the microtubule in one orientation, while ATP binding gives each step its direction through a process known as neck linker zippering<ref name="Rice">{{cite journal|author= 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 | title = A structural change in the kinesin motor protein that drives motility | journal = Nature | date = 1999 | volume = 402 | pages = 778–784 | doi = 10.1038/45483}}</ref>. 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''. A different type of motor protein known as [[dynein]]s, 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{{Fact|date=April 2008}}. ==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<ref name="Yildiz et al">{{cite journal|author= Yildiz A, Tomishige M, Vale RD, Selvin PR | title = Kinesin Walks Hand-Over-Hand | journal = Science | date = 2004 | volume = 303 | pages = 676–8 | pmid = 14684828|doi= 10.1126/science.1093753}}</ref><ref name="Asbury">{{cite journal|author= Asbury CL | title = Kinesin: world’s tiniest biped | journal = Current Opinion in Cell Biology | date = 2005 | volume = 17 | pages = 89–97 | pmid = 15661524|doi= 10.1016/j.ceb.2004.12.002}}</ref>. ==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 [[M Type Kinesins|Kinesin 13]] family act as regulators of microtubule dynamics. The prototypical member of this family is MCAK (formerly Kif2C, XKCM1, Gene {{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== <gallery> Image:Motility of kinesin.png|Motility of kinesin </gallery> ==See also== *[[Molecular motors]] *[[Dynein]] *[[Kinesin 8]] *[[Kinesin 13]] *[[Axoplasmic transport]] == References == <references/> ==External links== *[http://valelab.ucsf.edu/ Animated model of kinesin walking] *[http://tissue.medicalengineer.co.uk/Cellular+Motility+in+Brief.php Kinesin and Dynein Microtubule Movement] *[http://www.studiodaily.com/main/technique/tprojects/6850.html The Inner Life of a Cell, 3D animation featuring a Kinesin transporting a vesicle] *[http://www.proweb.org/~kinesin/ The Kinesin Homepage] *{{MeshName|Kinesin}} *{{EC number|3.6.4.4}} *{{EC number|3.6.4.5}} *Kinesin Nomenclature {{Entrez Pubmed|15479732}} {{Cytoskeletal Proteins}} {{ATPases}} [[Category:Motor proteins]] [[ca:Cinesina]] [[de:Kinesin]] [[es:Kinesina]] [[fr:Kinésine]] [[it:Chinesina]] [[ja:キネシン]] [[pl:Kinezyny]] [[pt:Cinesina]] [[zh:驱动蛋白]]