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The N‐terminus of myosin binding protein‐C diminishes the Ca 2+ dependence of the rate of tension redevelopment in permeabilized cardiac trabeculae
Author(s) -
Harris Samantha,
Razumova Maria V,
Bezold Kristina L,
Tu Anyue,
Regnier Michael
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.963.4
Subject(s) - biophysics , recombinant dna , myosin , linker , chemistry , protein filament , microbiology and biotechnology , crystallography , biology , biochemistry , computer science , gene , operating system
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 (c) MyBP‐C on contractile properties of permeabilized rat cardiac trabeculae. Here we show that N‐terminal fragments of cMyBP‐C containing the first two immunoglobulin (Ig) domains of cMyBP‐C (i.e., C0 and C1) plus the unique linker sequence termed the MyBP‐C “motif” increased Ca 2+ sensitivity of tension and increased rates of tension redevelopment (i.e., k tr ) at sub‐maximal levels of Ca 2+ . Rates of tension redevelopment were accelerated to near maximal even at the lowest levels of force generation, thus significantly diminishing the Ca 2+ ‐dependence of k tr . At concentrations ≥20 μM, recombinant proteins also activated force in the absence of Ca 2+ (pCa 9.0) and inhibited maximum Ca 2+ ‐activated force at pCa 4.5. 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 cooperatively activates the thin filament. This work supported by NIH HL080367 (to SPH) and HL 061683 (to MR).