Limits...
Myosin binding protein C: implications for signal-transduction.

Knöll R - J. Muscle Res. Cell. Motil. (2011)

Bottom Line: While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood.However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play.Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure.

View Article: PubMed Central - PubMed

Affiliation: Imperial College, National Heart and Lung Institute, British Heart Foundation-Centre for Research Excellence, Myocardial Genetics, London, UK. r.knoell@imperial.ac.uk

ABSTRACT
Myosin binding protein C (MYBPC) is a crucial component of the sarcomere and an important regulator of muscle function. While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood. A variety of MYBPC3 (cardiac isoform) mutations have been studied in great detail and several corresponding genetically altered mouse models have been generated. Most MYBPC3 mutations may cause haploinsufficiency and with it they may cause a primary increase in calcium sensitivity which is potentially able to explain major features observed in HCM patients such as the hypercontractile phenotype and the well known secondary effects such as myofibrillar disarray, fibrosis, myocardial hypertrophy and remodelling including arrhythmogenesis. However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play. Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure.

Show MeSH

Related in: MedlinePlus

Summarizes the major differences between the MYBPC models proposed by (Moolman-Smook et al. 2002) (a) and (Squire et al. 2003) (b). Please note in a MYBPC forms a “trimeric collar” that constrains the thick filament (Moolman-Smook et al. 2002). Top: schematic diagram showing a single MYBPC protein interacting with myosin (“top view”), bottom: side view. Whereas in b the carboxyterminal end of MYBPC is aligned axially (Squire et al. 2003). Top view: a thick filament is represented along with six surrounding actin filaments (in striated muscle), the broken circle represents the C0 domain in the MYBPC3 isoform. Bottom: side view, domains C7–C10 running axially along the myosin filament backbone. A few myosin heads are drawn as “transparent” ghosts to indicate their position (grey circles: MYBPC3 with green indicating the P/A rich domain; yellow/brown: myosin, dark grey: actin; figures are from: (Squire et al. 2003) with kind permission from the authors and the publisher (Journal of Molecular Biology))
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3351598&req=5

Fig3: Summarizes the major differences between the MYBPC models proposed by (Moolman-Smook et al. 2002) (a) and (Squire et al. 2003) (b). Please note in a MYBPC forms a “trimeric collar” that constrains the thick filament (Moolman-Smook et al. 2002). Top: schematic diagram showing a single MYBPC protein interacting with myosin (“top view”), bottom: side view. Whereas in b the carboxyterminal end of MYBPC is aligned axially (Squire et al. 2003). Top view: a thick filament is represented along with six surrounding actin filaments (in striated muscle), the broken circle represents the C0 domain in the MYBPC3 isoform. Bottom: side view, domains C7–C10 running axially along the myosin filament backbone. A few myosin heads are drawn as “transparent” ghosts to indicate their position (grey circles: MYBPC3 with green indicating the P/A rich domain; yellow/brown: myosin, dark grey: actin; figures are from: (Squire et al. 2003) with kind permission from the authors and the publisher (Journal of Molecular Biology))

Mentions: In addition, domains in the mid-region (C5–C8) have been hypothesized to interact with one another, forming a “trimeric collar” that constrains the thick filament (Moolman-Smook et al. 2002). Also, a slightly different model of MYBPC organisation within the sarcomere has been proposed by Squire et al. (2003). These authors due to structural considerations and because domains C7–C10 are also reported to interact with titin, which is unlikely to run other than axially along the myosin filament, propose a model whereby the carboxyterminal end of MYBPC is aligned axially, which contrasts the collar alignment structure (Fig. 3).Fig. 3


Myosin binding protein C: implications for signal-transduction.

Knöll R - J. Muscle Res. Cell. Motil. (2011)

Summarizes the major differences between the MYBPC models proposed by (Moolman-Smook et al. 2002) (a) and (Squire et al. 2003) (b). Please note in a MYBPC forms a “trimeric collar” that constrains the thick filament (Moolman-Smook et al. 2002). Top: schematic diagram showing a single MYBPC protein interacting with myosin (“top view”), bottom: side view. Whereas in b the carboxyterminal end of MYBPC is aligned axially (Squire et al. 2003). Top view: a thick filament is represented along with six surrounding actin filaments (in striated muscle), the broken circle represents the C0 domain in the MYBPC3 isoform. Bottom: side view, domains C7–C10 running axially along the myosin filament backbone. A few myosin heads are drawn as “transparent” ghosts to indicate their position (grey circles: MYBPC3 with green indicating the P/A rich domain; yellow/brown: myosin, dark grey: actin; figures are from: (Squire et al. 2003) with kind permission from the authors and the publisher (Journal of Molecular Biology))
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351598&req=5

Fig3: Summarizes the major differences between the MYBPC models proposed by (Moolman-Smook et al. 2002) (a) and (Squire et al. 2003) (b). Please note in a MYBPC forms a “trimeric collar” that constrains the thick filament (Moolman-Smook et al. 2002). Top: schematic diagram showing a single MYBPC protein interacting with myosin (“top view”), bottom: side view. Whereas in b the carboxyterminal end of MYBPC is aligned axially (Squire et al. 2003). Top view: a thick filament is represented along with six surrounding actin filaments (in striated muscle), the broken circle represents the C0 domain in the MYBPC3 isoform. Bottom: side view, domains C7–C10 running axially along the myosin filament backbone. A few myosin heads are drawn as “transparent” ghosts to indicate their position (grey circles: MYBPC3 with green indicating the P/A rich domain; yellow/brown: myosin, dark grey: actin; figures are from: (Squire et al. 2003) with kind permission from the authors and the publisher (Journal of Molecular Biology))
Mentions: In addition, domains in the mid-region (C5–C8) have been hypothesized to interact with one another, forming a “trimeric collar” that constrains the thick filament (Moolman-Smook et al. 2002). Also, a slightly different model of MYBPC organisation within the sarcomere has been proposed by Squire et al. (2003). These authors due to structural considerations and because domains C7–C10 are also reported to interact with titin, which is unlikely to run other than axially along the myosin filament, propose a model whereby the carboxyterminal end of MYBPC is aligned axially, which contrasts the collar alignment structure (Fig. 3).Fig. 3

Bottom Line: While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood.However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play.Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure.

View Article: PubMed Central - PubMed

Affiliation: Imperial College, National Heart and Lung Institute, British Heart Foundation-Centre for Research Excellence, Myocardial Genetics, London, UK. r.knoell@imperial.ac.uk

ABSTRACT
Myosin binding protein C (MYBPC) is a crucial component of the sarcomere and an important regulator of muscle function. While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood. A variety of MYBPC3 (cardiac isoform) mutations have been studied in great detail and several corresponding genetically altered mouse models have been generated. Most MYBPC3 mutations may cause haploinsufficiency and with it they may cause a primary increase in calcium sensitivity which is potentially able to explain major features observed in HCM patients such as the hypercontractile phenotype and the well known secondary effects such as myofibrillar disarray, fibrosis, myocardial hypertrophy and remodelling including arrhythmogenesis. However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play. Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure.

Show MeSH
Related in: MedlinePlus