Kinesin
Encyclopedia
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

 filaments, and are powered by the hydrolysis of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 (thus kinesins are ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

s). The active movement of kinesins supports several cellular functions including mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

, meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....

 and transport of cellular cargo, such as in axonal transport. Most kinesins walk towards the plus 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.

The Kinesins

Kinesins were discovered as microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

 (MT)-based anterograde intracellular transport motors. The founding member of this superfamily, kinesin-1, was isolated as a heterotetrameric fast axonal organelle transport motor consisting of 2 identical motor subunits (KHC) and 2 "light chains" (KLC) via microtubule affinity purification from neuronal cell extracts. Subsequently a different, heterotrimeric plus-end-directed MT-based motor named kinesin-2, consisting of 2 distinct KHC-related motor subunits and an accessory "KAP" subunit, was purified from echinoderm egg/embryo extracts and is best known for its role in transporting protein complexes (IFT particles) along axonemes during cilium
Cilium
A cilium is an organelle found in eukaryotic cells. Cilia are slender protuberances that project from the much larger cell body....

 biogenesis
Biogenesis
Biogenesis is the law that living things come only from other living things, e.g. a spider lays eggs, which develop into spiders. It may also refer to biochemical processes of production in living organisms.-Spontaneous generation:...

. Molecular genetic and genomic approaches have led to the recognition that the kinesins form a diverse superfamily of motors that are responsible for multiple intracellular motility events in eukaryotic cells. For example, the genomes of mammals encode more than 40 kinesin proteins, organized into at least 14 families named kinesin-1 through kinesin-14.

Overall structure

Members of the kinesin superfamily vary in shape but the prototypical kinesin-1 is a heterotetramer whose motor subunits (heavy chains or KHCs) form a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...

 (molecule pair) that binds two light chains (KLCs).

The heavy chain of kinesin-1 comprises a globular head (the motor domain) at the amino terminal end connected via a short, flexible neck linker to the stalk – a long, central alpha-helical coiled-coil domain – that ends in a carboxy terminal tail domain which associates with the light-chains. The stalks of two KHCs intertwine to form a coiled-coil that directs dimerization of the two KHCs. In most cases transported cargo binds to the kinesin light chains, but in some cases cargo binds to the C-terminal domains of the heavy chains.

Kinesin motor domain

The head is the signature of kinesin and its amino acid sequence is well conserved among various kinesins. Each head has two separate binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...

s: one for the microtubule and the other for ATP. ATP binding and hydrolysis as well as ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 release change the conformation of the microtubule-binding domains and the orientation of the neck linker 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
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 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
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 diffuse
Brownian motion
Brownian motion or pedesis is the presumably random drifting of particles suspended in a fluid or the mathematical model used to describe such random movements, which is often called a particle theory.The mathematical model of Brownian motion has several real-world applications...

 to where they are needed. Large molecules synthesised in the cell body, intracellular components such as vesicle
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

s, and organelles such as mitochondria are too large (and the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 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
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

 tracks hydrolysing one molecule of adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 (ATP) at each step. It was thought that ATP hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 powered each step, the energy released propelling the head forwards to the next binding site. However, it has been proposed that the head diffuses forward and the force of binding to the microtubule is what pulls the cargo along.

There is significant evidence that cargoes in-vivo are transported by multiple motors.

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.

Most kinesins walk towards the plus 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. Kinesin-14 family proteins, such as Drosophila NCD, budding yeast KAR3, and Arabidopsis ATK5, walk in the opposite direction, toward microtubule minus ends.

A different type of motor protein known as dynein
Dynein
Dynein is a motor protein in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell...

s, move towards the minus end of the microtubule. Thus they transport cargo from the periphery of the cell towards the centre, for example from the terminal buttons of a neuronal axon to the cell body (soma). This is known as retrograde transport.

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.

ATP binding and hydrolysis cause kinesin to travel via a "seesaw mechanism" about a pivot point.

Theoretical modeling of kinesin

A number of theoretical models of the molecular motor protein Kinesin have been proposed. Many challenges are encountered in theoretical investigations given the remaining uncertainties about the roles of protein structures, precise way energy from ATP is transformed into mechanical work, and the roles played by thermal fluctuations. This is a rather active area of research. There is a need especially for approaches which better make a link with the molecular architecture of the protein and data obtained from experimental investigations.

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
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 (cell division). Kinesins are important for proper spindle length and are involved in sliding microtubules apart within the spindle during prometaphase and metaphase, as well as depolymerizing microtubule minus ends at centrosomes during anaphase. Specifically, Kinesin-5 family proteins act within the spindle to slide microtubules apart, while the Kinesin 13
M Type Kinesins
The Kinesin-13 Family are a subfamily of motor proteins known as kinesins. Most kinesins transport materials or cargo around the cell while traversing along microtubule polymer tracks with the help of ATP-hydrolysis-created energy...

 family act to depolymerize microtubules.

Kinesin Superfamily members

Human kinesin superfamily members include the following proteins, which in the standardized nomenclature developed by the community of kinesin researchers, are organized into 14 families named kinesin-1 through kinesin-14:
  • 1A – KIF1A
    KIF1A
    Kinesin-like protein KIF1A, also known as axonal transporter of synaptic vesicles or microtubule-based motor KIF1A, is a protein that in humans is encoded by the KIF1A gene.- Function :KIF1A is a member of the kinesin family...

    , 1B – KIF1B
    KIF1B
    Kinesin-like protein KIF1B is a protein that in humans is encoded by the KIF1B gene.-External links:*...

     = kinesin-3
  • 2A – KIF2A
    KIF2A
    Kinesin-like protein KIF2A is a protein that in humans is encoded by the KIF2A gene.-Further reading:...

    , 2C – KIF2C
    KIF2C
    Kinesin-like protein KIF2C is a protein that in humans is encoded by the KIF2C gene.-Further reading:...

     = kinesin-13
  • 3B – KIF3B
    KIF3B
    Kinesin-like protein KIF3B is a protein that in humans is encoded by the KIF3B gene.- Function :The protein encoded by this gene forms a heterotrimeric motor complex with kinesin family member 3A and KAP3 to drive intra-flagellar transport and possibly to aid in chromosome movement during mitosis...

    , 3C – KIF3C
    KIF3C
    Kinesin-like protein KIF3C is a protein that in humans is encoded by the KIF3C gene.-Further reading:...

     = kinesin-2
  • 4A – KIF4A
    KIF4A
    Chromosome-associated kinesin KIF4A is a protein that in humans is encoded by the KIF4A gene.-Interactions:KIF4A has been shown to interact with HMG20B and DNMT3B.-Further reading:...

    , 4B – KIF4B = kinesin-4
  • 5A – KIF5A
    KIF5A
    Kinesin heavy chain isoform 5A is a protein that in humans is encoded by the KIF5A gene.-Further reading:...

    , 5B – KIF5B
    KIF5B
    Kinesin-1 heavy chain is a protein that in humans is encoded by the KIF5B gene.-Interactions:KIF5B has been shown to interact with SNAP-25, SNAP23, KLC2, YWHAH and KLC1.-Further reading:...

    , 5C – KIF5C
    KIF5C
    Kinesin heavy chain isoform 5C is a protein that in humans is encoded by the KIF5C gene.-Further reading:...

     = kinesin-1
  • 6 – KIF6 = kinesin-9
  • 7 – KIF7 = kinesin-4
  • 9 – KIF9 = kinesin-9
  • 11 – KIF11 = kinesin-5
  • 12 – KIF12 = kinesin-12
  • 13A – KIF13A
    KIF13A
    Kinesin-like protein KIF13A is a protein that in humans is encoded by the KIF13A gene.-Further reading:...

    , 13B – KIF13B = kinesin-3
  • 14 – KIF14
    KIF14
    Kinesin-like protein KIF14 is a protein that in humans is encoded by the KIF14 gene.-Further reading:...

     = kinesin-3
  • 15 – KIF15 = kinesin-12
  • 16B – KIF16B = kinesin-3
  • 17 – KIF17
    KIF17
    Kinesin-like protein KIF17 is a protein that in humans is encoded by the KIF17 gene. KIF17 and its close relative, C. elegans OSM-3, are members of the kinesin-2 family of plus-end directed microtubule-based motor proteins. In contrast to heterotrimeric kinesin-2 motors, however, KIF17 and OSM-3...

     = kinesin-2
  • 18A – KIF18A
    KIF18A
    Kinesin-like protein KIF18A is a protein that in humans is encoded by the KIF18A gene.-Further reading:...

    , 18B – KIF18B = kinesin-8
  • 19 – KIF19 = kinesin-8
  • 20A – KIF20A
    KIF20A
    Kinesin-like protein KIF20A is a protein that in humans is encoded by the KIF20A gene.-Further reading:...

    , 20B – KIF20B = kinesin-6
  • 21A – KIF21A
    KIF21A
    Kinesin-like protein KIF21A is a protein that in humans is encoded by the KIF21A gene.- External links :* **...

    , 21B – KIF21B = kinesin-4
  • 22 – KIF22
    KIF22
    Kinesin-like protein KIF22 is a protein that in humans is encoded by the KIF22 gene.-Further reading:...

     = kinesin-10
  • 23 – KIF23
    KIF23
    Kinesin-like protein KIF23 is a protein that in humans is encoded by the KIF23 gene.- Function :The protein encoded by this gene is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during...

     = kinesin-6
  • 24 – KIF24
    KIF24
    Kinesin-like protein KIF24 is a protein that in humans is encoded by the KIF24 gene.-Further reading:...

     = kinesin-13
  • 25 – KIF25 = kinesin-14
  • 26A – KIF26A, 26B – KIF26B = kinesin-11
  • 27 – KIF27 = kinesin-4
  • C1 – KIFC1
    KIFC1
    Kinesin-like protein KIFC1 is a protein that in humans is encoded by the KIFC1 gene.-Further reading:...

    , C2 – KIFC2, C3 – KIFC3
    KIFC3
    Kinesin-like protein KIFC3 is a protein that in humans is encoded by the KIFC3 gene.-Further reading:...

     = kinesin-14


kinesin-1 light chains:
  • 1 – KLC1
    KLC1
    Kinesin light chain 1 is a protein that in humans is encoded by the KLC1 gene.-Interactions:KLC1 has been shown to interact with MAPK8IP3, KIF5B and KIF5A.-Further reading:...

    , 2 – KLC2
    KLC2
    Kinesin light chain 2 is a protein that in humans is encoded by the KLC2 gene.-Interactions:KLC2 has been shown to interact with MAPK8IP3 and KIF5B.-Further reading:...

    , 3 – KLC3
    KLC3
    Kinesin light chain 3 is a protein that in humans is encoded by the KLC3 gene.-Further reading:...

    , 4 – KLC4
    KLC4
    Kinesin light chain 4 is a protein that in humans is encoded by the KLC4 gene.-Further reading:...



kinesin-2 associated protein:
  • KAP-1, KAP3 or KIFAP3

See also

  • Axoplasmic transport
    Axoplasmic transport
    Axoplasmic transport, also called axonal transport, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other cell parts to and from a neuron's cell body, through the cytoplasm of its axon...

  • Dynein
    Dynein
    Dynein is a motor protein in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell...

  • Intraflagellar transport
    Intraflagellar transport
    Intraflagellar transport or IFT is a bidirectional motility along axonemal microtubules that is essential for the formation and maintenance of most eukaryotic cilia and flagella. It is thought to be required to build all cilia that assemble within a membrane projection from the cell surface...

     along cilia
  • Kinesin 8
    Kinesin 8
    The Kinesin 8 Family are a subfamily of the molecular motor proteins known as kinesins. Most kinesins transport materials or cargo around the cell while traversing along microtubule polymer tracks with the help of ATP-hydrolysis-created energy. The Kinesin 8 family has been shown to play an...

  • Kinesin 13
  • KRP
    KRP
    KRP stands for kinesin related proteins. bimC is a subfamily of KRPs and its function is to separate the duplicated centrosomes during mitosis....

  • Molecular motors
    Molecular motors
    Molecular motors are biological molecular machines that are the essential agents of movement in living organisms. Generally speaking, a motor may be defined as a device that consumes energy in one form and converts it into motion or mechanical work; for example, many protein-based molecular motors...

  • Transport by Multiple Kinesin

External links

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