Investigating the effects of mutations within the coiled-coil tail of cardiac and skeletal myosin

Abstract

Myosin is an essential driver of cardiac and skeletal muscle function. Multiple mutations identified in β-cardiac/skeletal slow myosin heavy chain (MYH7) and skeletal fast myosin heavy chain 2A (MYH2), cause a group of human skeletal muscle diseases termed myosinopathies. Over 90% of these mutations are found in the filament-forming region of the coiled-coil tail, also known as light meromyosin (LMM). Mutation to a proline residue or deletion of a single residue are common. Both are predicted to strongly affect the secondary structure of the coiled coil, and by extension their incorporation into the thick filament.