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Kinesin
A kinesin is a protein complex belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzyme). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport, and intraflagellar transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the minus end of a microtubule in retrograde transport.[citation needed]
The first kinesins to be discovered were microtubule-based anterograde intracellular transport motors in 1985, based on their motility in cytoplasm extruded from the giant axon of the squid.
The founding member of this superfamily, kinesin-1, was isolated as a heterotetrameric fast axonal organelle transport motor consisting of four parts: two identical motor subunits (called Kinesin Heavy Chain (KHC) molecules) and two other molecules each known as a Kinesin Light Chain (KLC). These were discovered via microtubule affinity purification from neuronal cell extracts. Subsequently, a different, heterotrimeric plus-end-directed MT-based motor named kinesin-2, consisting of two 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 (intraflagellar transport particles) along axonemes during ciliogenesis. 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.
Members of the kinesin superfamily vary in shape but the prototypical kinesin-1 motor consists of two Kinesin Heavy Chain (KHC) molecules which form a protein dimer (molecule pair) that binds two light chains (KLCs), which are unique for different cargos.[citation needed]
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, at the TPR motif sequence of the KLC, but in some cases cargo binds to the C-terminal domains of the heavy chains.
The head is the signature of kinesin and its amino acid sequence is well conserved among various kinesins. 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 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 structurally related 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 domain.
Kinesins tend to have low basal enzymatic activity which becomes significant when microtubule-activated. In addition, many members of the kinesin superfamily can be self-inhibited by the binding of tail domain to the motor domain. Such self-inhibition can then be relieved via additional regulation such as binding to cargo, cargo adapters or other microtubule-associated proteins.
In the cell, small molecules, such as gases and glucose, diffuse to where they are needed.[citation 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 be able 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. It was thought that ATP hydrolysis 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. In addition viruses, HIV for example, exploit kinesins to allow virus particle shuttling after assembly.
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Kinesin AI simulator
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Kinesin
A kinesin is a protein complex belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzyme). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport, and intraflagellar transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the minus end of a microtubule in retrograde transport.[citation needed]
The first kinesins to be discovered were microtubule-based anterograde intracellular transport motors in 1985, based on their motility in cytoplasm extruded from the giant axon of the squid.
The founding member of this superfamily, kinesin-1, was isolated as a heterotetrameric fast axonal organelle transport motor consisting of four parts: two identical motor subunits (called Kinesin Heavy Chain (KHC) molecules) and two other molecules each known as a Kinesin Light Chain (KLC). These were discovered via microtubule affinity purification from neuronal cell extracts. Subsequently, a different, heterotrimeric plus-end-directed MT-based motor named kinesin-2, consisting of two 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 (intraflagellar transport particles) along axonemes during ciliogenesis. 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.
Members of the kinesin superfamily vary in shape but the prototypical kinesin-1 motor consists of two Kinesin Heavy Chain (KHC) molecules which form a protein dimer (molecule pair) that binds two light chains (KLCs), which are unique for different cargos.[citation needed]
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, at the TPR motif sequence of the KLC, but in some cases cargo binds to the C-terminal domains of the heavy chains.
The head is the signature of kinesin and its amino acid sequence is well conserved among various kinesins. 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 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 structurally related 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 domain.
Kinesins tend to have low basal enzymatic activity which becomes significant when microtubule-activated. In addition, many members of the kinesin superfamily can be self-inhibited by the binding of tail domain to the motor domain. Such self-inhibition can then be relieved via additional regulation such as binding to cargo, cargo adapters or other microtubule-associated proteins.
In the cell, small molecules, such as gases and glucose, diffuse to where they are needed.[citation 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 be able 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. It was thought that ATP hydrolysis 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. In addition viruses, HIV for example, exploit kinesins to allow virus particle shuttling after assembly.