Unknown

Dataset Information

0

Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck?


ABSTRACT: Myosin-binding protein C (MyBP-C) is a multidomain protein present in the thick filaments of striated muscles and is involved in both sarcomere formation and contraction regulation. The latter function is believed to be located at the N terminus, which is close to the motor domain of myosin. The cardiac isoform of MyBP-C is linked to hypertrophic cardiomyopathy. Here, we use NMR spectroscopy and biophysical and biochemical assays to study the three-dimensional structure and interactions of the cardiac-specific Ig-like domain C0, a part of cardiac MyBP-C of which little is known. The structure confirmed that C0 is a member of the IgI class of proteins, showing many of the characteristic features of this fold. Moreover, we identify a novel interaction between C0 and the regulatory light chain of myosin, thus placing the N terminus of the protein in proximity to the motor domain of myosin. This novel interaction is disrupted by several cardiomyopathy-linked mutations in the MYBPC3 gene. These results provide new insights into how cardiac MyBP-C incorporates in the sarcomere and how it can contribute to the regulation of muscle contraction.

SUBMITTER: Ratti J 

PROVIDER: S-EPMC3069465 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck?

Ratti Joyce J   Rostkova Elena E   Gautel Mathias M   Pfuhl Mark M  

The Journal of biological chemistry 20110205 14


Myosin-binding protein C (MyBP-C) is a multidomain protein present in the thick filaments of striated muscles and is involved in both sarcomere formation and contraction regulation. The latter function is believed to be located at the N terminus, which is close to the motor domain of myosin. The cardiac isoform of MyBP-C is linked to hypertrophic cardiomyopathy. Here, we use NMR spectroscopy and biophysical and biochemical assays to study the three-dimensional structure and interactions of the c  ...[more]

Similar Datasets

| S-EPMC8230336 | biostudies-literature
| S-EPMC2631168 | biostudies-literature
| S-EPMC8301185 | biostudies-literature
| S-EPMC5308206 | biostudies-literature
| S-EPMC4297556 | biostudies-literature
| S-EPMC3374655 | biostudies-literature
| S-EPMC1200277 | biostudies-literature
| S-EPMC3935486 | biostudies-literature
| S-EPMC8733265 | biostudies-literature
| S-EPMC1852638 | biostudies-literature