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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: 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.

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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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: 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.

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