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Contribution of the myosin binding protein C motif to functional effects in permeabilized rat trabeculae.

Razumova MV, Bezold KL, Tu AY, Regnier M, Harris SP - J. Gen. Physiol. (2008)

Bottom Line: Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output.Recombinant proteins that lacked the combination of C1 and the motif did not affect contractile properties.These results suggest that the C1 domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

ABSTRACT
Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output. To investigate mechanisms by which MyBP-C affects contraction, we assessed effects of recombinant N-terminal domains of cardiac MyBP-C (cMyBP-C) on contractile properties of permeabilized rat cardiac trabeculae. Here, we show that N-terminal fragments of cMyBP-C that contained the first three immunoglobulin domains of cMyBP-C (i.e., C0, C1, and C2) plus the unique linker sequence termed the MyBP-C "motif" or "m-domain" increased Ca(2+) sensitivity of tension and increased rates of tension redevelopment (i.e., k(tr)) at submaximal levels of Ca(2+). At concentrations > or =20 microM, recombinant proteins also activated force in the absence of Ca(2+) and inhibited maximum Ca(2+)-activated force. Recombinant proteins that lacked the combination of C1 and the motif did not affect contractile properties. These results suggest that the C1 domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.

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Related in: MedlinePlus

Schematic diagram showing the domain organization of cMyBP-C. (Top) Full-length cMyBP-C. (Bottom) Recombinant proteins used in this study.
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fig1: Schematic diagram showing the domain organization of cMyBP-C. (Top) Full-length cMyBP-C. (Bottom) Recombinant proteins used in this study.

Mentions: Myosin binding protein C (MyBP-C) is a sarcomeric protein comprised of repeating domains that are homologous to either Ig or fibronectin type III domains (Einheber and Fischman, 1990; Furst et al., 1992; Gautel et al., 1995). Skeletal isoforms of MyBP-C contain 10 such domains, termed C1 through C10, whereas cardiac MyBP-C (cMyBP-C) contains an additional Ig domain at its N terminus, referred to as C0 (see Fig. 1). Between domains C1 and C2 is a linker sequence, termed the MyBP-C “motif,” that is highly conserved among the different MyBP-C isoforms (Gautel et al., 1995).


Contribution of the myosin binding protein C motif to functional effects in permeabilized rat trabeculae.

Razumova MV, Bezold KL, Tu AY, Regnier M, Harris SP - J. Gen. Physiol. (2008)

Schematic diagram showing the domain organization of cMyBP-C. (Top) Full-length cMyBP-C. (Bottom) Recombinant proteins used in this study.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2571974&req=5

fig1: Schematic diagram showing the domain organization of cMyBP-C. (Top) Full-length cMyBP-C. (Bottom) Recombinant proteins used in this study.
Mentions: Myosin binding protein C (MyBP-C) is a sarcomeric protein comprised of repeating domains that are homologous to either Ig or fibronectin type III domains (Einheber and Fischman, 1990; Furst et al., 1992; Gautel et al., 1995). Skeletal isoforms of MyBP-C contain 10 such domains, termed C1 through C10, whereas cardiac MyBP-C (cMyBP-C) contains an additional Ig domain at its N terminus, referred to as C0 (see Fig. 1). Between domains C1 and C2 is a linker sequence, termed the MyBP-C “motif,” that is highly conserved among the different MyBP-C isoforms (Gautel et al., 1995).

Bottom Line: Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output.Recombinant proteins that lacked the combination of C1 and the motif did not affect contractile properties.These results suggest that the C1 domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

ABSTRACT
Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output. To investigate mechanisms by which MyBP-C affects contraction, we assessed effects of recombinant N-terminal domains of cardiac MyBP-C (cMyBP-C) on contractile properties of permeabilized rat cardiac trabeculae. Here, we show that N-terminal fragments of cMyBP-C that contained the first three immunoglobulin domains of cMyBP-C (i.e., C0, C1, and C2) plus the unique linker sequence termed the MyBP-C "motif" or "m-domain" increased Ca(2+) sensitivity of tension and increased rates of tension redevelopment (i.e., k(tr)) at submaximal levels of Ca(2+). At concentrations > or =20 microM, recombinant proteins also activated force in the absence of Ca(2+) and inhibited maximum Ca(2+)-activated force. Recombinant proteins that lacked the combination of C1 and the motif did not affect contractile properties. These results suggest that the C1 domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.

Show MeSH
Related in: MedlinePlus