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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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Relative effects of proteins containing C1 and the MyBP-C motif on Ca2+ sensitivity of tension. Tension–pCa relationships were determined after incubation of trabeculae with 5 μM C1m (upward triangles; n = 6), 5 μM C1C2 (diamonds; n = 4), 5 μM C0C1m (squares; n = 4), and 5 μM C0C2 (downward triangles; n = 6). Data for C1m and C0C1m were redrawn from Fig. 4. Controls curves (circles) were obtained in each trabecula before the addition of recombinant protein.
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fig5: Relative effects of proteins containing C1 and the MyBP-C motif on Ca2+ sensitivity of tension. Tension–pCa relationships were determined after incubation of trabeculae with 5 μM C1m (upward triangles; n = 6), 5 μM C1C2 (diamonds; n = 4), 5 μM C0C1m (squares; n = 4), and 5 μM C0C2 (downward triangles; n = 6). Data for C1m and C0C1m were redrawn from Fig. 4. Controls curves (circles) were obtained in each trabecula before the addition of recombinant protein.

Mentions: Fig. 5 shows a comparison of the force–pCa relationships for proteins containing the C1 and m-domains. The relative efficacy of the different proteins as assessed by the midpoint shift in force–pCa relations (i.e., ΔpCa50) was C0C2 > C0C1m ≥ C1C2 > C1m. Thus, although C1m was the minimal subunit capable of inducing a leftward shift of the force–pCa relationship, it was not as effective as proteins containing either the C0 or C2 domains in addition to C1m. Summary data for effects of the different proteins are shown in Table I.


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)

Relative effects of proteins containing C1 and the MyBP-C motif on Ca2+ sensitivity of tension. Tension–pCa relationships were determined after incubation of trabeculae with 5 μM C1m (upward triangles; n = 6), 5 μM C1C2 (diamonds; n = 4), 5 μM C0C1m (squares; n = 4), and 5 μM C0C2 (downward triangles; n = 6). Data for C1m and C0C1m were redrawn from Fig. 4. Controls curves (circles) were obtained in each trabecula before the addition of recombinant protein.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Relative effects of proteins containing C1 and the MyBP-C motif on Ca2+ sensitivity of tension. Tension–pCa relationships were determined after incubation of trabeculae with 5 μM C1m (upward triangles; n = 6), 5 μM C1C2 (diamonds; n = 4), 5 μM C0C1m (squares; n = 4), and 5 μM C0C2 (downward triangles; n = 6). Data for C1m and C0C1m were redrawn from Fig. 4. Controls curves (circles) were obtained in each trabecula before the addition of recombinant protein.
Mentions: Fig. 5 shows a comparison of the force–pCa relationships for proteins containing the C1 and m-domains. The relative efficacy of the different proteins as assessed by the midpoint shift in force–pCa relations (i.e., ΔpCa50) was C0C2 > C0C1m ≥ C1C2 > C1m. Thus, although C1m was the minimal subunit capable of inducing a leftward shift of the force–pCa relationship, it was not as effective as proteins containing either the C0 or C2 domains in addition to C1m. Summary data for effects of the different proteins are shown in Table I.

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