Sandbox Reserved 473: Difference between revisions

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== Structure ==

The structure of several kinesins have been elucidated primarily by X-ray crystallography, but also by electron microscopy [7]. The structure of conventional kinesin, a particular type of kinesin so named because it has been the most studied, is displayed at right. Conventional kinesin is a homodimer composed of two subunits, each with a heavy-chain (KHC) and light-chain (KLC) domain <ref>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>~~[4]~~. Together, these units form a protein composed of three main regions: the head, the stalk, and the tail. (NEED A FIGURE) 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 head, also known as the motor domain or the heavy chain, is responsible for microtubule binding and catalytic activity. This motor domain is the most conserved element among all kinesins, with 35% sequence homology across all kinesins ~~[4]~~. The stalk and tail share little homology, suggesting the diversity of cargo that different kinesins bind ~~[4]~~.

The structure of several kinesins have been elucidated primarily by X-ray crystallography, but also by electron microscopy [7]. The structure of conventional kinesin, a particular type of kinesin so named because it has been the most studied, is displayed at right. Conventional kinesin is a homodimer composed of two subunits, each with a heavy-chain (KHC) and light-chain (KLC) domain <ref>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. (NEED A FIGURE) 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 head, also known as the motor domain or the heavy chain, is responsible for microtubule binding and catalytic activity. This 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>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/2'>ATP/ADP binding site</scene>, the neck and neck linker, and the relay helix. 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 ~~[4]~~.

Key features within the motor domain include the <scene name='Sandbox_Reserved_473/Atp_binding_site/2'>ATP/ADP binding site</scene>, the neck and neck linker, and the relay helix. 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>Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>.

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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 ADP 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 neck linker to “zipper” into a binding pocket in the motor domain (near a structure called the relay helix). The zippering causes the second head of the kinesin to swing around and land on the microtubule ahead of the first head [6]. The second head may reach the microtubule either by active movement, by simple diffusion, or by a combination of the two ~~[4]~~. 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 [2].

In solution or in a free state, kinesin has ADP 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 neck linker to “zipper” into a binding pocket in the motor domain (near a structure called the relay helix). The zippering causes the second head of the kinesin to swing around and land on the microtubule ahead of the first head [6]. The second head may reach the microtubule either by active movement, by simple diffusion, or by a combination of the two <ref>Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>. 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 [2].

The reaction repeats over and over again as the kinesin binds and hydrolyzes one ATP for each 8-nanometer step it takes [5]. Once bound to the microtubule, kinesin can take several steps without falling off, an ability known as processivity.

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=== 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 [6]. 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>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>. 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 ~~[4]~~.

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 [6]. 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>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>. 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>Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>.

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@@ Line 12: / Line 12: @@
 == Structure ==
-The structure of several kinesins have been elucidated primarily by X-ray crystallography, but also by electron microscopy [7]. The structure of conventional kinesin, a particular type of kinesin so named because it has been the most studied, is displayed at right. Conventional kinesin is a homodimer composed of two subunits, each with a heavy-chain (KHC) and light-chain (KLC) domain <ref>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>[4]. Together, these units form a protein composed of three main regions: the head, the stalk, and the tail. (NEED A FIGURE) 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 head, also known as the motor domain or the heavy chain, is responsible for microtubule binding and catalytic activity. This motor domain is the most conserved element among all kinesins, with 35% sequence homology across all kinesins [4]. The stalk and tail share little homology, suggesting the diversity of cargo that different kinesins bind [4].
+The structure of several kinesins have been elucidated primarily by X-ray crystallography, but also by electron microscopy [7]. The structure of conventional kinesin, a particular type of kinesin so named because it has been the most studied, is displayed at right. Conventional kinesin is a homodimer composed of two subunits, each with a heavy-chain (KHC) and light-chain (KLC) domain <ref>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. (NEED A FIGURE) 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 head, also known as the motor domain or the heavy chain, is responsible for microtubule binding and catalytic activity. This 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>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/2'>ATP/ADP binding site</scene>, the neck and neck linker, and the relay helix. 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 [4].
+Key features within the motor domain include the <scene name='Sandbox_Reserved_473/Atp_binding_site/2'>ATP/ADP binding site</scene>, the neck and neck linker, and the relay helix. 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>Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>.
@@ Line 24: / Line 24: @@
 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 ADP 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 neck linker to “zipper” into a binding pocket in the motor domain (near a structure called the relay helix). The zippering causes the second head of the kinesin to swing around and land on the microtubule ahead of the first head [6]. The second head may reach the microtubule either by active movement, by simple diffusion, or by a combination of the two [4]. 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 [2].
+In solution or in a free state, kinesin has ADP 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 neck linker to “zipper” into a binding pocket in the motor domain (near a structure called the relay helix). The zippering causes the second head of the kinesin to swing around and land on the microtubule ahead of the first head [6]. The second head may reach the microtubule either by active movement, by simple diffusion, or by a combination of the two <ref>Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>. 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 [2].
 The reaction repeats over and over again as the kinesin binds and hydrolyzes one ATP for each 8-nanometer step it takes [5]. Once bound to the microtubule, kinesin can take several steps without falling off, an ability known as processivity.
@@ Line 31: / Line 31: @@
 === 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 [6]. 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>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>. 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 [4].
+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 [6]. 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>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>. 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>Woehlke, G. and Schliwa, M. (2000.) Walking on two heads: the many talents of kinesin. Nature Rev. Mol. Cell Biol. 1, 50-58.</ref>.