Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)




The goal of my dissertation was to compare and contrast the function of all three major isoforms of Myosin Binding Protein-C (MyBP-C): slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C, and cMyBP-C, respectively), with a focus on the least characterized isoform, fsMyBP-C. Using a variety of ex vivo, in vitro, and in silico methods, my research demonstrated that the N-terminal region of all MyBP-C isoforms bind to actin and shift tropomyosin, thus activating the thin filament during contraction. Furthermore, each isoform differentially activated the thin filament over isoform-specific ranges of Ca2+: slow-skeletal activates at low Ca2+, fast-skeletal activates at higher Ca2+, and cardiac activates over the full spectrum of Ca2+. I propose that different expression of MyBP-C isoforms allow striated muscles to fine tune its function. For example, the cardiac muscle sees the full range of Ca2+ on a beat-to-beat basis, and therefore cMyBP-C needs to operate over the full spectrum of Ca2+ with much higher frequency. Conversely, various skeletal muscles have vastly different roles: the demands of postural muscles are different than that of phasic muscles; thus, varied expression of slow-skeletal and fast-skeletal MyBP-C can ideally regulate the function of different muscles.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Included in

Biophysics Commons