Fig. 7.

Locations of 17 hypertrophic cardiomyopathy mutations in the myosin catalytic domain. (A) Cartoon showing two groups of HCM mutations. Four mutations are in the converter domain (dark green), and 13 are on or very near the myosin mesa (bright green). Sixteen of the HCM mutations were chosen because they have been documented to be the cause of HCM in families carrying these mutations (Alfares et al., 2015). The 17th is M531R, which, while only documented in one family, is a left ventricular non-compaction mutant myosin that appears to be hypercontractile in our studies. (B) The top view of the mesa showing 13 mutations on or near the mesa surface. The residues labeled in blue denote the positively charged amino acids. (C) The same view as in B except the surface charge distribution is shown. I263T, N444S, and M531R are slightly below the surface in acidic pockets, while the remainder of the mutations are on or very near the surface and most are arginine residues, seven of which form a particularly large domain of positive charge on the right half of the mesa as viewed.