Investigating the Effects of Mutations within the Coiled-Coil Tail of Cardiac and Skeletal Myosin

Myosin is an essential driver of cardiac and skeletal muscle function. Multiple mutations identified in β-cardiac/skeletal slow myosin heavy chain (MYH7) fast 2A (MYH2), cause a group human diseases termed myosinopathies1. Over 90% these are found the filament-forming region coiled-coil tail, also known as light meromyosin (LMM). A mutation to proline residue or deletion single-residue common mutations, both which predicted strongly affect secondary structure coiled coil, by extension their incorporation into thick filament.Using combination circular dichroism (CD) molecular dynamics (MD), we have begun unravel effects on structure, well investigate macro-structure filament vitro cells. We generated homology model full length using our recent cryo-EM smooth shutdown state2 interpret potential tail.Taken together, speculate destabilise resulting aberrant packing filaments sarcomeres, providing mechanism for disease.