Group:MUZIC:CapZ: Difference between revisions

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== Structure ==

CapZ was shown to be a heterodimer with α and β subunits of 286 and 277 residues, respectively. It is a mixed α-helix and β-sheet protein. CapZ has an elongated structure, with overall dimensions of~90 x 50 x55 Å. The CapZ dimer has a pseudo two-fold symmetry, with the monomers joining together to form a central 10-stranded antiparallel <scene name='User:Mara_Camelia_Rusu/Workbench/CapZ/Central_b_sheet/1'>a central 10-stranded β-sheet</scene>. ~~This creates an elongated molecule with the~~ N- and C-terminus of each monomer on opposite faces of the central β -sheet. The C-termini of the subdomains are at opposite ends of the elongated molecule.

CapZ was shown to be a heterodimer with α and β subunits of 286 and 277 residues, respectively. It is a mixed α-helix and β-sheet protein. CapZ has an elongated structure, with overall dimensions of~90 x 50 x55 Å. The CapZ dimer has a pseudo two-fold symmetry, with the monomers joining together to form a central 10-stranded antiparallel <scene name='User:Mara_Camelia_Rusu/Workbench/CapZ/Central_b_sheet/1'>a central 10-stranded β-sheet</scene>. The N- and C-terminus of each monomer are on opposite faces of the central β -sheet. The C-termini of the subdomains are at opposite ends of the elongated molecule.

One CapZ heterodimer ~~appears to be able to bind~~ two actin molecules; this may explain why it is selective for the F-actin barbed end as opposed to monomeric G-actin. CapZ is thought to bind between actin subdomains 1 and 3 (the barbed-end). CapZ also binds a spectrin domain of α-actinin and the C-terminus of nebulin <ref>PMID:15583864</ref>.

One CapZ heterodimer binds two actin molecules; this may explain why it is selective for the F-actin barbed end as opposed to monomeric G-actin. CapZ is thought to bind between actin subdomains 1 and 3 (the barbed-end). CapZ also binds a spectrin domain of α-actinin and the C-terminus of nebulin <ref>PMID:15583864</ref>.

== Function and Interactions==

Capping protein binds to the barbed end with high affinity (Kd > 1 nM) ~~and the stoichiometry is~~ 1:1 and it prevents the loss and addition of actin monomers. CapZ is important in the dynamics of actin filaments ~~as it~~ is crucial for rapid filament elongation as a response to signaling. It does so by blocking the barbed ends, thus ensuring a high steady state concentration of G-actin in the cytoplasm <ref>PMID:12660160</ref>. The absence of capping protein prevented the reconstruction of motility in ''Shigella'' and ''Listeria'', ''in vitro''.

Capping protein binds to the barbed end with high affinity (Kd > 1 nM) with 1:1 stoichiometry and prevents the loss and addition of actin monomers. CapZ is important in the dynamics of actin filaments and is crucial for rapid filament elongation as a response to signaling. It does so by blocking the barbed ends, thus ensuring a high steady state concentration of G-actin in the cytoplasm <ref>PMID:12660160</ref>. The absence of capping protein prevented the reconstruction of motility in Shigella and Listeria, in vitro. CapZ plays a role in targeting the actin filaments to other structural components. The sarcomeric isoform interacts with α-actinin and anchors the thin filament system to the Z-disk <ref>PMID:16416311</ref>. Small interference RNA (siRNA) studies showed that knockdown of nebulin in chick skeletal myotubes leads to a reduction of assembled CapZ and a loss of the characteristic uniform alignment of the barbed ends of F-actin and this suggests that the interaction of CapZ and nebulin plays an important role in Z-disk architecture <ref>PMID:18272787</ref>. CapZ regulates the activity of cardiac protein kinase C (PKC): down regulation of CapZ leads to a decrease and alteration of the PKC signaling pathways. Cardiac CapZ regulates binding of PKC II to the myofilaments with effects on cardiac contractility <ref>PMID:21257757</ref>. Other binding partners of CapZ include the CARMIL protein, which further interacts with Arp complex2/3 and myosin I, both of which are key players in actin based cell motility <ref>PMID:12660160</ref>. In vivo the capping of actin filaments is regulated by second messengers PIP and PIP 2 (Phosphatidylinositol 4,5-bisphosphate), upon signal transduction these molecules promote removal of CapZ from actin filaments <ref>PMID:12663865</ref>.

CapZ plays a role in targeting the actin filaments to other structural components. The sarcomeric isoform interacts with α-actinin and anchors the thin filament system to the Z-disk <ref>PMID:16416311</ref>

Small interference RNA (siRNA) studies showed that knockdown of nebulin in chick skeletal myotubes leads to a reduction of assembled CapZ and a loss of the characteristic uniform alignment of the barbed ends of F-actin and this suggests that the interaction of CapZ and nebulin plays ~~a very~~ important role in Z-disk architecture <ref>PMID:18272787</ref>.

CapZ regulates the activity of cardiac protein kinase C (PKC): down regulation of CapZ leads to a decrease and alteration of the PKC signaling pathways. Cardiac CapZ regulates binding of PKC II to the myofilaments with effects on cardiac contractility <ref>PMID:21257757</ref>.

Other binding partners of CapZ include the CARMIL protein which further interacts with Arp complex2/3 and myosin I, both of which are key players in actin based cell motility <ref>PMID:12660160</ref>.

In vivo the capping of actin filaments is regulated by second messengers PIP and PIP 2 (Phosphatidylinositol 4,5-bisphosphate), upon signal transduction these molecules promote removal of CapZ from actin filaments <ref>PMID:12663865</ref>.

== Actin binding model ==

Group:MUZIC:CapZ: Difference between revisions

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 == Structure ==
-CapZ was shown to be a heterodimer with α and β subunits of 286 and 277 residues, respectively. It is a mixed α-helix and β-sheet protein. CapZ has an elongated structure, with overall dimensions of~90 x 50 x55 Å. The CapZ dimer has a pseudo two-fold symmetry, with the monomers joining together to form a central 10-stranded antiparallel <scene name='User:Mara_Camelia_Rusu/Workbench/CapZ/Central_b_sheet/1'>a central 10-stranded β-sheet</scene>. This creates an elongated molecule with the N- and C-terminus of each monomer on opposite faces of the central β -sheet. The C-termini of the subdomains are at opposite ends of the elongated molecule.
+CapZ was shown to be a heterodimer with α and β subunits of 286 and 277 residues, respectively. It is a mixed α-helix and β-sheet protein. CapZ has an elongated structure, with overall dimensions of~90 x 50 x55 Å. The CapZ dimer has a pseudo two-fold symmetry, with the monomers joining together to form a central 10-stranded antiparallel <scene name='User:Mara_Camelia_Rusu/Workbench/CapZ/Central_b_sheet/1'>a central 10-stranded β-sheet</scene>. The N- and C-terminus of each monomer are on opposite faces of the central β -sheet. The C-termini of the subdomains are at opposite ends of the elongated molecule.
-One CapZ heterodimer appears to be able to bind two actin molecules; this may explain why it is selective for the F-actin barbed end as opposed to monomeric G-actin. CapZ is thought to bind between actin subdomains 1 and 3 (the barbed-end). CapZ also binds a spectrin domain of α-actinin and  the C-terminus of nebulin <ref>PMID:15583864</ref>.
+One CapZ heterodimer binds two actin molecules; this may explain why it is selective for the F-actin barbed end as opposed to monomeric G-actin. CapZ is thought to bind between actin subdomains 1 and 3 (the barbed-end). CapZ also binds a spectrin domain of α-actinin and  the C-terminus of nebulin <ref>PMID:15583864</ref>.
 == Function and Interactions==
-Capping protein binds to the barbed end with high affinity (Kd > 1 nM) and the stoichiometry is 1:1 and it prevents the loss and addition of actin monomers. CapZ is important in the dynamics of actin filaments as it is crucial for rapid filament elongation as a response to signaling. It does so by blocking the barbed ends, thus ensuring a high steady state concentration of G-actin in the cytoplasm <ref>PMID:12660160</ref>. The absence of capping protein prevented the reconstruction of motility in ''Shigella'' and ''Listeria'', ''in vitro''.
+Capping protein binds to the barbed end with high affinity (Kd > 1 nM) with 1:1 stoichiometry and prevents the loss and addition of actin monomers. CapZ is important in the dynamics of actin filaments and is crucial for rapid filament elongation as a response to signaling. It does so by blocking the barbed ends, thus ensuring a high steady state concentration of G-actin in the cytoplasm <ref>PMID:12660160</ref>. The absence of capping protein prevented the reconstruction of motility in Shigella and Listeria, in vitro. CapZ plays a role in targeting the actin filaments to other structural components. The sarcomeric isoform interacts with α-actinin and anchors the thin filament system to the Z-disk <ref>PMID:16416311</ref>. Small interference RNA (siRNA) studies showed that knockdown of nebulin in chick skeletal myotubes leads to a reduction of assembled CapZ and a loss of the characteristic uniform alignment of the barbed ends of F-actin and this suggests that the interaction of CapZ and nebulin plays an important role in Z-disk architecture <ref>PMID:18272787</ref>. CapZ regulates the activity of cardiac protein kinase C (PKC): down regulation of CapZ leads to a decrease and alteration of the PKC signaling pathways. Cardiac CapZ regulates binding of PKC II to the myofilaments with effects on cardiac contractility <ref>PMID:21257757</ref>. Other binding partners of CapZ include the CARMIL protein, which further interacts with Arp complex2/3 and myosin I, both of which are key players in actin based cell motility <ref>PMID:12660160</ref>. In vivo the capping of actin filaments is regulated by second messengers PIP and PIP 2 (Phosphatidylinositol 4,5-bisphosphate), upon signal transduction these molecules promote removal of CapZ from actin filaments <ref>PMID:12663865</ref>.
-CapZ plays a role in targeting the actin filaments to other structural components. The sarcomeric isoform interacts with α-actinin and anchors the thin filament system to the Z-disk <ref>PMID:16416311</ref>
-Small interference RNA (siRNA) studies showed that knockdown of nebulin in chick skeletal myotubes leads to a reduction of assembled CapZ and a loss of the characteristic uniform alignment of the barbed ends of F-actin and this suggests that the interaction of CapZ and nebulin plays a very important role in Z-disk architecture <ref>PMID:18272787</ref>.
-CapZ regulates the activity of cardiac protein kinase C (PKC): down regulation of CapZ leads to a decrease and alteration of the PKC signaling pathways. Cardiac CapZ regulates binding of PKC II to the myofilaments with effects on cardiac contractility <ref>PMID:21257757</ref>.
-Other binding partners of CapZ include the CARMIL protein which further interacts with Arp complex2/3 and myosin I, both of which are key players in actin based cell motility <ref>PMID:12660160</ref>.
-In vivo the capping of actin filaments is regulated by second messengers PIP and PIP 2 (Phosphatidylinositol 4,5-bisphosphate), upon signal transduction these molecules promote removal of CapZ from actin filaments <ref>PMID:12663865</ref>.
 == Actin binding model ==