Figure S4.

Structural model of K104E mutation in M2α-S1. The effect of the K104E mutation in the RLC is depicted in the structural model of modified M2α-S1 (HBCprestrokeS1 Homology Model, Spudich Lab, Stanford University, Stanford, CA). (A) The murine α-MHC (Myh6, cyan) and the murine RLC (Myl1, purple) were threaded through the model of human cardiac S1 (http://spudlab.stanford.edu/homology-models) using Chimera Modeller (zDOPE scores = −0.47 and −0.71, respectively). The human isoform of K104E (red) was threaded through and overlaid upon the human WT isoform (blue). The IQ motifs (yellow) represent the sites of light chain binding to the lever arm. (B) Magnified view of overlaid WT and K104E RLC from inset in A. The N-terminal lobe of K104E is not predicted to shift in the model (left, nearly perfect overlap), while the C-terminal lobe shifts significantly (right), such that K104E is more closely associated to the lever arm. Yellow dotted lines indicate distance from functional groups of lysine (K104, blue) and glutamate (K104E, red) to nearby carbon of isoleucine, the first residue of the IQ motif, which measure 11.0 Å and 4.5 Å, respectively.