cMyBPC organization and C0–C2 mutants tested. (A) Full-length cMyBP-C domains C0–C10. Ig-like domains shown as circles and Fn3-like domains as hexagons. (B) C0–C2 domains containing P/A linker and phosphorylatable M-domain are shown. Sequence of M-domain and locations of HCM mutations tested for binding. PKA phosphorylatable Ser residues are in green, PKA recognition sequences are indicated with underlines, and HCM mutation sites are in red. Helix residues in the tri-helix bundle are indicated with thick underlines. Structure insets: tri-helix bundle (Michie et al., 2016; PDB accession no. 5K6P) containing L352P and E334K mutations and C1 (Risi et al., 2018; PDBaccession no. 6CXI) showing the RASK loop between adjacent β-strands that interacts with Tm. (C) C0–C1 is a deletion of the M-domain and C2.