Limits...
Fishing out proteins that bind to titin.

Sanger JW, Sanger JM - J. Cell Biol. (2001)

Bottom Line: Like titin, obscurin contains multiple immunoglobulin-like domains linked in tandem, but in contrast to titin it contains just two fibronectin-like domains.During embryonic development, its localization changes from the Z-band to the M-band.With these intriguing properties, obscurin may not remain obscure for long.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. sangerj@mail.med.upenn.edu

ABSTRACT
Another giant protein has been detected in cross-striated muscle cells. Given the name obscurin, it was discovered in a yeast two-hybrid screen in which the bait was a small region of titin that is localized near the Z-band. Obscurin is about 720 kD, similar in molecular weight to nebulin, but present at about one tenth the level (Young et al., 2001). Like titin, obscurin contains multiple immunoglobulin-like domains linked in tandem, but in contrast to titin it contains just two fibronectin-like domains. It also contains sequences that suggest obscurin may have roles in signal transduction. During embryonic development, its localization changes from the Z-band to the M-band. With these intriguing properties, obscurin may not remain obscure for long.

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Diagram of a sarcomere bounded by the Z-bands. The left side of the sarcomere represents a half sarcomere found in vertebrate skeletal myofibrils. Note that the nebulin molecules are part of and extend the entire length of the thin filaments. The right side of the sarcomere reflects a half sarcomere in cardiac muscle cells. The smaller nebulin isoform, nebulette, begins within the Z-band and extends only a short distance along the thin filament. Titin is shown with its NH2 termini from adjacent sarcomeres overlapping in the Z-band. Groups of three titin filaments are shown aligned together in the half sarcomere and overlapping in the M-band with groups of three from the other half sarcomere. The scale of the drawing does not allow the ratio of six titins per half-thick filament or the two nebulin isoforms per actin thin filament to be illustrated. The double-headed arrows indicate the position of the region of titin used as a bait to pull out obscurin. The M-band is the mid-point of the group of aligned thick myosin filaments (A-band) where obscurin binds in cultured neonatal cardiomyocytes and in adult muscles.
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fig1: Diagram of a sarcomere bounded by the Z-bands. The left side of the sarcomere represents a half sarcomere found in vertebrate skeletal myofibrils. Note that the nebulin molecules are part of and extend the entire length of the thin filaments. The right side of the sarcomere reflects a half sarcomere in cardiac muscle cells. The smaller nebulin isoform, nebulette, begins within the Z-band and extends only a short distance along the thin filament. Titin is shown with its NH2 termini from adjacent sarcomeres overlapping in the Z-band. Groups of three titin filaments are shown aligned together in the half sarcomere and overlapping in the M-band with groups of three from the other half sarcomere. The scale of the drawing does not allow the ratio of six titins per half-thick filament or the two nebulin isoforms per actin thin filament to be illustrated. The double-headed arrows indicate the position of the region of titin used as a bait to pull out obscurin. The M-band is the mid-point of the group of aligned thick myosin filaments (A-band) where obscurin binds in cultured neonatal cardiomyocytes and in adult muscles.

Mentions: The basic unit that provides the structural framework for contraction of cross-striated muscles is the sarcomere (Fig. 1) . In order for the myosin thick filaments and the interdigitating actin filaments to interact optimally and generate force, many other proteins of the sarcomere are required. The two largest proteins in the sarcomere, nebulin and titin, help link the actin and myosin filaments in the sarcomere. The thin actin filaments are tethered in the Z-band, a dense substructure that is home to several known and unknown proteins and the site where the ends of titin filaments and nebulin molecules are also embedded. In vertebrate skeletal muscles (Fig. 1, left), 800 kD nebulin has its COOH terminus embedded in the Z-band. Two nebulin molecules extend along the length of each 1-μm long actin filament to form a thin filament (Labeit and Kolmerer, 1995a). Titin, the largest known protein at 3–3.7 million D has its NH2 terminus embedded in the Z-band and extends for 1 μm with its COOH terminus localized in the middle (M-band) of the aligned myosin filaments (A-band). Thus, each Z-band has two sets of overlapping NH2-terminal titin ends, and the M-band has two sets of overlapping COOH-terminal titin ends. The titin filaments are elastic and attach the thick filaments to the Z-bands (for review see Gregorio et al., 1999). Recent work by Liversage et al. (2001) using scanning transmission electron microscopy indicates that there may be just six titin filaments per half myosin filament, that is, each myosin filament binding to two sets of six overlapping oppositely polarized titin filaments.


Fishing out proteins that bind to titin.

Sanger JW, Sanger JM - J. Cell Biol. (2001)

Diagram of a sarcomere bounded by the Z-bands. The left side of the sarcomere represents a half sarcomere found in vertebrate skeletal myofibrils. Note that the nebulin molecules are part of and extend the entire length of the thin filaments. The right side of the sarcomere reflects a half sarcomere in cardiac muscle cells. The smaller nebulin isoform, nebulette, begins within the Z-band and extends only a short distance along the thin filament. Titin is shown with its NH2 termini from adjacent sarcomeres overlapping in the Z-band. Groups of three titin filaments are shown aligned together in the half sarcomere and overlapping in the M-band with groups of three from the other half sarcomere. The scale of the drawing does not allow the ratio of six titins per half-thick filament or the two nebulin isoforms per actin thin filament to be illustrated. The double-headed arrows indicate the position of the region of titin used as a bait to pull out obscurin. The M-band is the mid-point of the group of aligned thick myosin filaments (A-band) where obscurin binds in cultured neonatal cardiomyocytes and in adult muscles.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196855&req=5

fig1: Diagram of a sarcomere bounded by the Z-bands. The left side of the sarcomere represents a half sarcomere found in vertebrate skeletal myofibrils. Note that the nebulin molecules are part of and extend the entire length of the thin filaments. The right side of the sarcomere reflects a half sarcomere in cardiac muscle cells. The smaller nebulin isoform, nebulette, begins within the Z-band and extends only a short distance along the thin filament. Titin is shown with its NH2 termini from adjacent sarcomeres overlapping in the Z-band. Groups of three titin filaments are shown aligned together in the half sarcomere and overlapping in the M-band with groups of three from the other half sarcomere. The scale of the drawing does not allow the ratio of six titins per half-thick filament or the two nebulin isoforms per actin thin filament to be illustrated. The double-headed arrows indicate the position of the region of titin used as a bait to pull out obscurin. The M-band is the mid-point of the group of aligned thick myosin filaments (A-band) where obscurin binds in cultured neonatal cardiomyocytes and in adult muscles.
Mentions: The basic unit that provides the structural framework for contraction of cross-striated muscles is the sarcomere (Fig. 1) . In order for the myosin thick filaments and the interdigitating actin filaments to interact optimally and generate force, many other proteins of the sarcomere are required. The two largest proteins in the sarcomere, nebulin and titin, help link the actin and myosin filaments in the sarcomere. The thin actin filaments are tethered in the Z-band, a dense substructure that is home to several known and unknown proteins and the site where the ends of titin filaments and nebulin molecules are also embedded. In vertebrate skeletal muscles (Fig. 1, left), 800 kD nebulin has its COOH terminus embedded in the Z-band. Two nebulin molecules extend along the length of each 1-μm long actin filament to form a thin filament (Labeit and Kolmerer, 1995a). Titin, the largest known protein at 3–3.7 million D has its NH2 terminus embedded in the Z-band and extends for 1 μm with its COOH terminus localized in the middle (M-band) of the aligned myosin filaments (A-band). Thus, each Z-band has two sets of overlapping NH2-terminal titin ends, and the M-band has two sets of overlapping COOH-terminal titin ends. The titin filaments are elastic and attach the thick filaments to the Z-bands (for review see Gregorio et al., 1999). Recent work by Liversage et al. (2001) using scanning transmission electron microscopy indicates that there may be just six titin filaments per half myosin filament, that is, each myosin filament binding to two sets of six overlapping oppositely polarized titin filaments.

Bottom Line: Like titin, obscurin contains multiple immunoglobulin-like domains linked in tandem, but in contrast to titin it contains just two fibronectin-like domains.During embryonic development, its localization changes from the Z-band to the M-band.With these intriguing properties, obscurin may not remain obscure for long.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. sangerj@mail.med.upenn.edu

ABSTRACT
Another giant protein has been detected in cross-striated muscle cells. Given the name obscurin, it was discovered in a yeast two-hybrid screen in which the bait was a small region of titin that is localized near the Z-band. Obscurin is about 720 kD, similar in molecular weight to nebulin, but present at about one tenth the level (Young et al., 2001). Like titin, obscurin contains multiple immunoglobulin-like domains linked in tandem, but in contrast to titin it contains just two fibronectin-like domains. It also contains sequences that suggest obscurin may have roles in signal transduction. During embryonic development, its localization changes from the Z-band to the M-band. With these intriguing properties, obscurin may not remain obscure for long.

Show MeSH
Related in: MedlinePlus