| First Author | Previs MJ | Year | 2012 |
| Journal | Science | Volume | 337 |
| Issue | 6099 | Pages | 1215-8 |
| PubMed ID | 22923435 | Mgi Jnum | J:187698 |
| Mgi Id | MGI:5437799 | Doi | 10.1126/science.1223602 |
| Citation | Previs MJ, et al. (2012) Molecular mechanics of cardiac myosin-binding protein C in native thick filaments. Science 337(6099):1215-8 |
| abstractText | The heart's pumping capacity results from highly regulated interactions of actomyosin molecular motors. Mutations in the gene for a potential regulator of these motors, cardiac myosin-binding protein C (cMyBP-C), cause hypertrophic cardiomyopathy. However, cMyBP-C's ability to modulate cardiac contractility is not well understood. Using single-particle fluorescence imaging techniques, transgenic protein expression, proteomics, and modeling, we found that cMyBP-C slowed actomyosin motion generation in native cardiac thick filaments. This mechanical effect was localized to where cMyBP-C resides within the thick filament (i.e., the C-zones) and was modulated by phosphorylation and site-specific proteolytic degradation. These results provide molecular insight into why cMyBP-C should be considered a member of a tripartite complex with actin and myosin that allows fine tuning of cardiac muscle contraction. |
