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= Kinesin =

== Introduction ==

Kinesin is a superfamily of motor proteins, one of three major known groups of molecular motors. The other two groups are myosin and dynein. These molecular motors convert chemical energy into mechanical energy through ATP hydrolysis for transport within the cell.

Kinesin is known for its directed “walking” motion along microtubules, which are key components of the cell cytoskeleton. Kinesin is believed to transport large cargo such as organelles, vesicles, and even chromosomes during mitosis and meiosis in most or all eukaryotic organisms <ref name = "goldstein"/>.

[[Image:3kin.png|thumb|left|Conventional kinesin motor domain]]

== Structure ==

The structure of several kinesins have been elucidated primarily by X-ray crystallography, and also partly by electron microscopy <ref>Kull, F. J., Sablin, E.P., Lau, R., Fletterick, R.J., and Vale, R.D. (1996.) Crystal structure of the kinesin motor domain reveals a structural similarity to myosin. Nature, 380: 550-55.</ref>. The structure of conventional kinesin, a particular type of kinesin so named because it has been the most studied, is displayed in both the 2D and 3D figures shown. Conventional kinesin is a homodimer composed of two subunits, each with a heavy-chain (KHC) and light-chain (KLC) domain <ref name = "goldstein">Goldstein, L.S.B. and Philp, A.V. (1999.) The road less traveled: emerging principles of kinesin motor utilization. Annu. Rev. Cell Dev. Biol. 15, 141-183.</ref>. Together, these units form a protein composed of three main regions: the head, the stalk, and the tail. The tail is responsible for binding the cargo. The stalk usually consists of a structure similar to a coiled coil that helps to secure the two monomers together. (The tail and stalk are not shown in the figures.) The head, also known as the motor domain or the heavy chain, is responsible for microtubule binding and catalytic activity. It is composed of several <scene name='Sandbox_Reserved_473/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_473/Beta/1'>beta sheets</scene>. The motor domain is the most conserved element among all kinesins, with 35% sequence homology across all kinesins. The stalk and tail share little homology, suggesting the diversity of cargo that different kinesins bind <ref name = "woehlke">Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>.

Key features within the motor domain include the <scene name='Sandbox_Reserved_473/Atp_binding_site/3'>ATP/ADP binding site</scene>, the <scene name='Sandbox_Reserved_473/Neck/2'>neck and neck linker</scene>, and the <scene name='Sandbox_Reserved_473/Relay_helix/1'>relay helix</scene>. The ATP-binding site consists of a P-loop motif common not only to kinesin, but also to myosin as well as several G-proteins which also have nucleotidase activity. This homology suggests a common ancestor among these proteins <ref name = "woehlke"/>.

== Mechanism ==

Molecular motors convert chemical energy to mechanical energy by causing reactions that power directed conformational changes, resulting in motion.

In solution or in a free state, kinesin has <scene name='Sandbox_Reserved_473/Atp_binding_site/3'>ADP</scene> bound to each head or motor domain. Once kinesin attaches to a microtubule and changes its conformation slightly, ADP can be exchanged for high-energy ATP. This action causes the <scene name='Sandbox_Reserved_473/Neck/2'>neck linker</scene> to “zipper” into a binding pocket in the motor domain (near a structure called the <scene name='Sandbox_Reserved_473/Relay_helix/1'>relay helix</scene>). The zippering causes the second head of the kinesin to swing around and land on the microtubule ahead of the first head <ref name = "movie">Milligan, R. (2000.) An animated model for processive motility by conventional kinesin (movie). Retrieved from http://www.scripps.edu/milligan/research/movies/kinesin_text.html</ref>. The second head may reach the microtubule either by active movement, by simple diffusion, or by a combination of the two <ref name = "woehlke"/>. While the second head binds the microtubule, ATP hydrolysis occurs at the first head, releasing it from the microtubule. ATP hydrolysis also “unzippers” the neck linker from the relay helix, resetting the conformation for another reaction. It is remarkable that ATP binding and hydrolysis create tiny conformational changes in the active site (on the order of angstroms) that can lead to large overall conformational changes in the entire protein (on the order of nanometers). This phenomenon is known as mechanical amplification <ref>Vale, R.D. and Milligan, R.A. (2000.) The way things move: looking under the hood of molecular motor proteins. Science 288(5463): 88-95.</ref>.

The reaction repeats over and over again as the kinesin binds and hydrolyzes one ATP for each 8-nanometer step it takes <ref name = "pdb">Goodsell, D. (2005.) Kinesin. RCSB Protein Data Bank. Retrieved from http://www.rcsb.org/pdb/101/motm.do?momID=64</ref>. Once bound to the microtubule, kinesin can take several steps without falling off, an ability known as processivity.

=== Directionality ===

Kinesins walk along microtubules, which are a key component of the cytoskeleton and are composed of heterodimers of α- and β-tubulin. A microtubule is in the shape of a hollow cylinder with a circumference of 13 tubulin units <ref name = "movie"/>. The heterodimers layer in a helical fashion, giving the microtubule polarity. The ends are labeled as plus and minus, with the minus-end typically anchored near the center of the cell at a centrosome, and the plus-ends branching out towards the cell membrane <ref name = "goldstein"/>. This polarity is critical for the directed movement of kinesin because it allows the kinesin to recognize the directionality of the microtubule and transport its cargo in the right direction. Kinesins travel in only one direction along the microtubule. Typically, they travel from the minus end to the plus end, but some kinesins (such as ncd) travel in the opposite direction <ref name = "woehlke"/>.

=== Regulation ===

Regulation of kinesin is not fully understood, but it is believed to occur at the cargo-binding tail or light chain (KLC) domain of the protein <ref name = "woehlke"/>.

== Applications ==

While kinesins are generally studied for understanding of structure, mechanism and function, kinesin might be implicated in several diseases in which defective transport occurs in cells. For instance, kinesin may be involved in causing the protein aggregation that leads to neurodegenerative diseases such as Alzheimer's. Better understanding of the mechanism of kinesin, and if and how it is responsible in causing these diseases, could lead to new treatments. Additionally, since kinesin is critically involved in cell replication through mitosis, it could be targeted in cancer treatments as a way to prevent cancer cell division <ref>Mandelkow, E. and Mandelkow, E.M. (2002.) Kinesin motors and disease. Trends in Cell Biol., 12(12): 585-91.</ref>.

== References ==

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@@ Line 2: / Line 2: @@
 {{Sandbox_Reserved_Robert_B_Rose_1}}
 <!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
+= Kinesin =
+== Introduction ==
+Kinesin is a superfamily of motor proteins, one of three major known groups of molecular motors. The other two groups are myosin and dynein. These molecular motors convert chemical energy into mechanical energy through ATP hydrolysis for transport within the cell.
+Kinesin is known for its directed “walking” motion along microtubules, which are key components of the cell cytoskeleton. Kinesin is believed to transport large cargo such as organelles, vesicles, and even chromosomes during mitosis and meiosis in most or all eukaryotic organisms <ref name = "goldstein"/>.
+[[Image:3kin.png|thumb|left|Conventional kinesin motor domain]]
+== Structure ==
+The structure of several kinesins have been elucidated primarily by X-ray crystallography, and also partly by electron microscopy <ref>Kull, F. J., Sablin, E.P., Lau, R., Fletterick, R.J., and Vale, R.D. (1996.) Crystal structure of the kinesin motor domain reveals a structural similarity to myosin. Nature, 380: 550-55.</ref>. The structure of conventional kinesin, a particular type of kinesin so named because it has been the most studied, is displayed in both the 2D and 3D figures shown. Conventional kinesin is a homodimer composed of two subunits, each with a heavy-chain (KHC) and light-chain (KLC) domain <ref name = "goldstein">Goldstein, L.S.B. and Philp, A.V. (1999.) The road less traveled: emerging principles of kinesin motor utilization. Annu. Rev. Cell Dev. Biol. 15, 141-183.</ref>. Together, these units form a protein composed of three main regions: the head, the stalk, and the tail. The tail is responsible for binding the cargo. The stalk usually consists of a structure similar to a coiled coil that helps to secure the two monomers together. (The tail and stalk are not shown in the figures.) The head, also known as the motor domain or the heavy chain, is responsible for microtubule binding and catalytic activity.  It is composed of several <scene name='Sandbox_Reserved_473/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_473/Beta/1'>beta sheets</scene>. The motor domain is the most conserved element among all kinesins, with 35% sequence homology across all kinesins. The stalk and tail share little homology, suggesting the diversity of cargo that different kinesins bind <ref name = "woehlke">Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>.
+Key features within the motor domain include the <scene name='Sandbox_Reserved_473/Atp_binding_site/3'>ATP/ADP binding site</scene>, the <scene name='Sandbox_Reserved_473/Neck/2'>neck and neck linker</scene>, and the <scene name='Sandbox_Reserved_473/Relay_helix/1'>relay helix</scene>. The ATP-binding site consists of a P-loop motif common not only to kinesin, but also to myosin as well as several G-proteins which also have nucleotidase activity. This homology suggests a common ancestor among these proteins <ref name = "woehlke"/>.
+<Structure load='3KIN' size='500' frame='true' align='right' caption='Conventional kinesin motor domain, PDB ID = 3kin' scene='Insert optional scene name here' />
+== Mechanism ==
+Molecular motors convert chemical energy to mechanical energy by causing reactions that power directed conformational changes, resulting in motion.
+In solution or in a free state, kinesin has <scene name='Sandbox_Reserved_473/Atp_binding_site/3'>ADP</scene> bound to each head or motor domain. Once kinesin attaches to a microtubule and changes its conformation slightly, ADP can be exchanged for high-energy ATP. This action causes the <scene name='Sandbox_Reserved_473/Neck/2'>neck linker</scene> to “zipper” into a binding pocket in the motor domain (near a structure called the <scene name='Sandbox_Reserved_473/Relay_helix/1'>relay helix</scene>). The zippering causes the second head of the kinesin to swing around and land on the microtubule ahead of the first head <ref name = "movie">Milligan, R. (2000.) An animated model for processive motility by conventional kinesin (movie). Retrieved from http://www.scripps.edu/milligan/research/movies/kinesin_text.html</ref>. The second head may reach the microtubule either by active movement, by simple diffusion, or by a combination of the two <ref name = "woehlke"/>. While the second head binds the microtubule, ATP hydrolysis occurs at the first head, releasing it from the microtubule. ATP hydrolysis also “unzippers” the neck linker from the relay helix, resetting the conformation for another reaction. It is remarkable that ATP binding and hydrolysis create tiny conformational changes in the active site (on the order of angstroms) that can lead to large overall conformational changes in the entire protein (on the order of nanometers). This phenomenon is known as mechanical amplification <ref>Vale, R.D. and Milligan, R.A. (2000.) The way things move: looking under the hood of molecular motor proteins. Science 288(5463): 88-95.</ref>.
+The reaction repeats over and over again as the kinesin binds and hydrolyzes one ATP for each 8-nanometer step it takes <ref name = "pdb">Goodsell, D. (2005.) Kinesin. RCSB Protein Data Bank. Retrieved from http://www.rcsb.org/pdb/101/motm.do?momID=64</ref>. Once bound to the microtubule, kinesin can take several steps without falling off, an ability known as processivity.
+=== Directionality ===
+Kinesins walk along microtubules, which are a key component of the cytoskeleton and are composed of heterodimers of α- and β-tubulin. A microtubule is in the shape of a hollow cylinder with a circumference of 13 tubulin units <ref name = "movie"/>. The heterodimers layer in a helical fashion, giving the microtubule polarity. The ends are labeled as plus and minus, with the minus-end typically anchored near the center of the cell at a centrosome, and the plus-ends branching out towards the cell membrane <ref name = "goldstein"/>. This polarity is critical for the directed movement of kinesin because it allows the kinesin to recognize the directionality of the microtubule and transport its cargo in the right direction. Kinesins travel in only one direction along the microtubule. Typically, they travel from the minus end to the plus end, but some kinesins (such as ncd) travel in the opposite direction <ref name = "woehlke"/>.
+=== Regulation ===
+Regulation of kinesin is not fully understood, but it is believed to occur at the cargo-binding tail or light chain (KLC) domain of the protein <ref name = "woehlke"/>.
+== Applications ==
+While kinesins are generally studied for understanding of structure, mechanism and function, kinesin might be implicated in several diseases in which defective transport occurs in cells. For instance, kinesin may be involved in causing the protein aggregation that leads to neurodegenerative diseases such as Alzheimer's. Better understanding of the mechanism of kinesin, and if and how it is responsible in causing these diseases, could lead to new treatments. Additionally, since kinesin is critically involved in cell replication through mitosis, it could be targeted in cancer treatments as a way to prevent cancer cell division <ref>Mandelkow, E. and Mandelkow, E.M. (2002.) Kinesin motors and disease. Trends in Cell Biol., 12(12): 585-91.</ref>.
+== References ==
+{{reflist}}