Group:MUZIC: Difference between revisions

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==Introduction==

Although all types of muscle cells use actin and myosin for contraction, only in skeletal and cardiac muscle these proteins are organized into sarcomeric units. They are generally composed of ordered thick (myosin) and thin (actin, tropomyosin, troponin) filaments that slide past each other during contraction. The precise ultra-structural order of these filaments is of utmost importance for converting the molecular interactions produced by actin and myosin in each sarcomere into efficient contraction at the macroscopic level (Figure 1). In addition to those components responsible for active muscle operation, many other filamentous proteins, such as titin and nebulin, have important roles in myofibril structure formation and regulation. Titin, the largest known vertebrate gene product, connects the Z-discs to the central M-band [reviewed in <ref>PMID:16337382</ref>] and nebulin, which spans the length of the actin filaments [reviewed in <ref name="r1">PMID:12142273</ref><ref>PMID:22375125</ref><ref>PMID:16230109</ref>].

Although all types of muscle cells use actin and myosin for contraction, only in skeletal and cardiac muscle these proteins are organized into sarcomeric units. They are generally composed of ordered thick (myosin) and thin (actin, tropomyosin, troponin) filaments that slide past each other during contraction. The precise ultra-structural order of these filaments is of utmost importance for converting the molecular interactions produced by actin and myosin in each sarcomere into efficient contraction at the macroscopic level ('''Figure 1'''). In addition to those components responsible for active muscle operation, many other filamentous proteins, such as titin and nebulin, have important roles in myofibril structure formation and regulation. Titin, the largest known vertebrate gene product, connects the Z-discs to the central M-band [reviewed in <ref>PMID:16337382</ref>] and nebulin, which spans the length of the actin filaments [reviewed in <ref name="r1">PMID:12142273</ref><ref>PMID:22375125</ref><ref>PMID:16230109</ref>].

One of the functionally most complex sub-compartments of the sarcomere is the Z-disc that forms the lateral boundaries between adjacent sarcomeres. This region plays a central role as the site organizing thick filaments and titin into the molecular machinery that is required for muscle contraction and comprises the actin, titin, and nebulin filaments.

Thin filaments (actin) from adjacent sarcomeres are anchored at the Z-disc. In this area of the sarcomere, each actin filament overlaps with four filaments from the opposite sarcomere, forming a square lattice, which is cross-connected in a zig-zag pattern by α-actinin-2 <ref>PMID:19830582</ref> (Figure 2). This region plays a central role as the main anchoring point of the molecular machinery for muscle contraction comprising the actin, titin, and nebulin filaments <ref>PMID:22028589</ref><ref>PMID:9476658</ref>.

Z-discs are also implicated in mechanosensing and signaling to the nucleus, which contribute to maintenance of muscle homeostasis, and serve as attachment sites for desmin intermediate filaments and often for transverse tubules [reviewed in <ref>PMID:12556452</ref><ref>PMID:21190822</ref><ref>PMID:21347754</ref>]. The assembly of the Z-disc is controlled via N-terminal part of titin, which exhibits binding sites for α-actinin-2 as well as to additional Z-disc components. The most striking feature of muscle and Z-disc proteins, in particular, is the diversity of multiple protein-protein interactions that form part of a complex network, involving more than forty proteins<ref name="r2">PMID:12142273</ref><ref>PMID:16416311</ref><ref>PMID:15810059</ref> (Figure 3). For example, titin binds to α-actinin-2 via 45-residue sequence motifs, the so-called Z-repeats <ref>PMID:9003807</ref> and dimerizes at its N-terminal through the mediator protein telethonin <ref>PMID:16407954</ref>.

[[Image:Sarcomere.png|left|600px]]

'''Figure 1''' ''Schematic overview of the basic muscle contractile unit: sarcomere. Myosin filaments are shown in the middle in blue. Actin filaments are depicted as orange helical structures at the top and bottom of the diagram. Titin with its elastic properties in its I-band region is indicated by symbolic coiling (in grey). Nebulin is shown in grey, wrapping around actin filaments. The Z-disc and the M-band comprise additional protein networks, as shown by grey areas, crosslinking individual filament systems.''

One of the functionally most complex sub-compartments of the sarcomere is the Z-disc that forms the lateral boundaries between adjacent sarcomeres. This region plays a central role as the site organizing thick filaments and titin into the molecular machinery that is required for muscle contraction and comprises the actin, titin, and nebulin filaments.

[[Image:Z-discmodelfigure last.jpg|left|800px]]

'''Figure 2''' ''Z-disk ultrastructure. (A) Antiparallel arrangement of actin filaments (grey) interconnected by several layers of α-actinin (green and red) forming an overlapping zigzag like structure (B) The same view rotated by 90deg. Figure was prepared by Dr Stephan Lange (UCSD) ''

Thin filaments (actin) from adjacent sarcomeres are anchored at the Z-disc. In this area of the sarcomere, each actin filament overlaps with four filaments from the opposite sarcomere, forming a square lattice, which is cross-connected in a zig-zag pattern by α-actinin-2 <ref>PMID:19830582</ref> ('''Figure 2'''). This region plays a central role as the main anchoring point of the molecular machinery for muscle contraction comprising the actin, titin, and nebulin filaments <ref>PMID:22028589</ref><ref>PMID:9476658</ref>.

Z-discs are also implicated in mechanosensing and signaling to the nucleus, which contribute to maintenance of muscle homeostasis, and serve as attachment sites for desmin intermediate filaments and often for transverse tubules [reviewed in <ref>PMID:12556452</ref><ref>PMID:21190822</ref><ref>PMID:21347754</ref>]. The assembly of the Z-disc is controlled via N-terminal part of titin, which exhibits binding sites for α-actinin-2 as well as to additional Z-disc components. The most striking feature of muscle and Z-disc proteins, in particular, is the diversity of multiple protein-protein interactions that form part of a complex network, involving more than forty proteins<ref name="r1">PMID:12142273</ref><ref>PMID:16416311</ref><ref>PMID:15810059</ref> ('''Figure 3'''). For example, titin binds to α-actinin-2 via 45-residue sequence motifs, the so-called Z-repeats <ref>PMID:9003807</ref> and dimerizes at its N-terminal through the mediator protein telethonin <ref>PMID:16407954</ref>.

[[Image:3d Z-disc.jpg|left|400px]]

'''Figure 3''' ''Virtual molecular model of the sarcomeric Z-disc, integrating selected presently known protein components<ref>PMID:18021935</ref>. Opposing thin filaments and individual titin molecules (pink, horizontal) interdigitate at the Z-disc and are cross-linked by α-actinin dimers (green) [http://www.e-heart.org/Pages/01_Cardiac_Structure/01_Cardiac_Structure_Molecular_Anatomy_003.htm www.e-heart.org]

==Links==

* Interactome [http://proteopedia.org/support/MUZIC (Flash version)] [[Group:MUZIC:Interactome|(static version) ]]

* [[Group:MUZIC:Protein_Index|Protein Index]] (browse proteins annotated by MUZIC)

==About MUZIC==

The MUZIC network provides a unique mix of cellular and structural biology laboratories with a focus on muscle research and combines a series of complementary state-of-the art know-how and technologies ranging from high resolution (X-ray crystallography) and low resolution structural biology methods (SAXS, EM, cryo-EM tomography, atomic force microscopy) to a variety of cell biology oriented techniques, ranging from FRET and live-cell imaging, cellular and animal models to animal physiology. These are complemented by a biochemical and biophysical ~~characterisation~~ of proteins and their complexes.

The '''MUZIC''' network provides a unique mix of cellular and structural biology laboratories with a focus on muscle research and combines a series of complementary state-of-the art know-how and technologies ranging from high resolution (X-ray crystallography) and low resolution structural biology methods (SAXS, EM, cryo-EM tomography, atomic force microscopy) to a variety of cell biology oriented techniques, ranging from FRET and live-cell imaging, cellular and animal models to animal physiology. These are complemented by a biochemical and biophysical characterization of proteins and their complexes.

[about_muzic]

[http://www.proteopedia.org/wiki/index.php/Group:MUZIC/about_muzic about_muzic]

==References==

@@ Line 2: / Line 2: @@
 ==Introduction==
-  Although all types of muscle cells use actin and myosin for contraction, only in skeletal and cardiac muscle these proteins are organized into sarcomeric units. They are generally composed of ordered thick (myosin) and thin (actin, tropomyosin, troponin) filaments that slide past each other during contraction. The precise ultra-structural order of these filaments is of utmost importance for converting the molecular interactions produced by actin and myosin in each sarcomere into efficient contraction at the macroscopic level (Figure 1). In addition to those components responsible for active muscle operation, many other filamentous proteins, such as titin and nebulin, have important roles in myofibril structure formation and regulation. Titin, the largest known vertebrate gene product, connects the Z-discs to the central M-band [reviewed in <ref>PMID:16337382</ref>] and nebulin, which spans the length of the actin filaments [reviewed in <ref name="r1">PMID:12142273</ref><ref>PMID:22375125</ref><ref>PMID:16230109</ref>].
+Although all types of muscle cells use actin and myosin for contraction, only in skeletal and cardiac muscle these proteins are organized into sarcomeric units. They are generally composed of ordered thick (myosin) and thin (actin, tropomyosin, troponin) filaments that slide past each other during contraction. The precise ultra-structural order of these filaments is of utmost importance for converting the molecular interactions produced by actin and myosin in each sarcomere into efficient contraction at the macroscopic level ('''Figure 1'''). In addition to those components responsible for active muscle operation, many other filamentous proteins, such as titin and nebulin, have important roles in myofibril structure formation and regulation. Titin, the largest known vertebrate gene product, connects the Z-discs to the central M-band [reviewed in <ref>PMID:16337382</ref>] and nebulin, which spans the length of the actin filaments [reviewed in <ref name="r1">PMID:12142273</ref><ref>PMID:22375125</ref><ref>PMID:16230109</ref>].
-  One of the functionally most complex sub-compartments of the sarcomere is the Z-disc that forms the lateral boundaries between adjacent sarcomeres. This region plays a central role as the site organizing thick filaments and titin into the molecular machinery that is required for muscle contraction and comprises the actin, titin, and nebulin filaments.
-  Thin filaments (actin) from adjacent sarcomeres are anchored at the Z-disc. In this area of the sarcomere, each actin filament overlaps with four filaments from the opposite sarcomere, forming a square lattice, which is cross-connected in a zig-zag pattern by α-actinin-2 <ref>PMID:19830582</ref> (Figure 2). This region plays a central role as the main anchoring point of the molecular machinery for muscle contraction comprising the actin, titin, and nebulin filaments <ref>PMID:22028589</ref><ref>PMID:9476658</ref>.
-  Z-discs are also implicated in mechanosensing and signaling to the nucleus, which contribute to maintenance of muscle homeostasis, and serve as attachment sites for desmin intermediate filaments and often for transverse tubules [reviewed in <ref>PMID:12556452</ref><ref>PMID:21190822</ref><ref>PMID:21347754</ref>]. The assembly of the Z-disc is controlled via N-terminal part of titin, which exhibits binding sites for α-actinin-2 as well as to additional Z-disc components. The most striking feature of muscle and Z-disc proteins, in particular, is the diversity of multiple protein-protein interactions that form part of a complex network, involving more than forty proteins<ref name="r2">PMID:12142273</ref><ref>PMID:16416311</ref><ref>PMID:15810059</ref> (Figure 3). For example, titin binds to α-actinin-2 via 45-residue sequence motifs, the so-called Z-repeats <ref>PMID:9003807</ref> and dimerizes at its N-terminal through the mediator protein telethonin <ref>PMID:16407954</ref>.
+[[Image:Sarcomere.png|left|600px]]
+'''Figure 1''' ''Schematic overview of the basic muscle contractile unit: sarcomere. Myosin filaments are shown in the middle in blue. Actin filaments are depicted as orange helical structures at the top and bottom of the diagram. Titin with its elastic properties in its I-band region is indicated by symbolic coiling (in grey). Nebulin is shown in grey, wrapping around actin filaments. The Z-disc and the M-band comprise additional protein networks, as shown by grey areas, crosslinking individual filament systems.''
+One of the functionally most complex sub-compartments of the sarcomere is the Z-disc that forms the lateral boundaries between adjacent sarcomeres. This region plays a central role as the site organizing thick filaments and titin into the molecular machinery that is required for muscle contraction and comprises the actin, titin, and nebulin filaments.
+[[Image:Z-discmodelfigure last.jpg|left|800px]]
+'''Figure 2''' ''Z-disk ultrastructure. (A) Antiparallel arrangement of actin filaments (grey) interconnected by several layers of α-actinin (green and red) forming an overlapping zigzag like structure (B) The same view rotated by 90deg. Figure was prepared by Dr Stephan Lange (UCSD) ''
+Thin filaments (actin) from adjacent sarcomeres are anchored at the Z-disc. In this area of the sarcomere, each actin filament overlaps with four filaments from the opposite sarcomere, forming a square lattice, which is cross-connected in a zig-zag pattern by α-actinin-2 <ref>PMID:19830582</ref> ('''Figure 2'''). This region plays a central role as the main anchoring point of the molecular machinery for muscle contraction comprising the actin, titin, and nebulin filaments <ref>PMID:22028589</ref><ref>PMID:9476658</ref>.
+Z-discs are also implicated in mechanosensing and signaling to the nucleus, which contribute to maintenance of muscle homeostasis, and serve as attachment sites for desmin intermediate filaments and often for transverse tubules [reviewed in <ref>PMID:12556452</ref><ref>PMID:21190822</ref><ref>PMID:21347754</ref>]. The assembly of the Z-disc is controlled via N-terminal part of titin, which exhibits binding sites for α-actinin-2 as well as to additional Z-disc components. The most striking feature of muscle and Z-disc proteins, in particular, is the diversity of multiple protein-protein interactions that form part of a complex network, involving more than forty proteins<ref name="r1">PMID:12142273</ref><ref>PMID:16416311</ref><ref>PMID:15810059</ref> ('''Figure 3'''). For example, titin binds to α-actinin-2 via 45-residue sequence motifs, the so-called Z-repeats <ref>PMID:9003807</ref> and dimerizes at its N-terminal through the mediator protein telethonin <ref>PMID:16407954</ref>.
+[[Image:3d Z-disc.jpg|left|400px]]
+'''Figure 3''' ''Virtual molecular model of the sarcomeric Z-disc, integrating selected presently known protein components<ref>PMID:18021935</ref>. Opposing thin filaments and individual titin molecules (pink, horizontal) interdigitate at the Z-disc and are cross-linked by α-actinin dimers (green) [http://www.e-heart.org/Pages/01_Cardiac_Structure/01_Cardiac_Structure_Molecular_Anatomy_003.htm www.e-heart.org]
+==Links==
+* Interactome [http://proteopedia.org/support/MUZIC (Flash version)]  [[Group:MUZIC:Interactome|(static version) ]]
+* [[Group:MUZIC:Protein_Index|Protein Index]] (browse proteins annotated by MUZIC)
 ==About MUZIC==
-The MUZIC network provides a unique mix of cellular and structural biology laboratories with a focus on muscle research and combines a series of complementary state-of-the art know-how and technologies ranging from high resolution (X-ray crystallography) and low resolution structural biology methods (SAXS, EM, cryo-EM tomography, atomic force microscopy) to a variety of cell biology oriented techniques, ranging from FRET and live-cell imaging, cellular and animal models to animal physiology. These are complemented by a biochemical and biophysical characterisation of proteins and their complexes.
+The '''MUZIC''' network provides a unique mix of cellular and structural biology laboratories with a focus on muscle research and combines a series of complementary state-of-the art know-how and technologies ranging from high resolution (X-ray crystallography) and low resolution structural biology methods (SAXS, EM, cryo-EM tomography, atomic force microscopy) to a variety of cell biology oriented techniques, ranging from FRET and live-cell imaging, cellular and animal models to animal physiology. These are complemented by a biochemical and biophysical characterization of proteins and their complexes.
-[about_muzic]
+[http://www.proteopedia.org/wiki/index.php/Group:MUZIC/about_muzic about_muzic]
 ==References==
 <references/>