Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism

摘要

Location of F437 and A234 residues on the myosin molecule. a Myosin sequences surrounding the F437 and A234 residues in human embryonic myosin are compared to their Drosophila counterparts. Identical residues are shown in red and conserved residues in blue. The mutations that cause DA are shown above the Drosophila sequences. b Myosin residues F437 (cyan) and A234 (green) of Drosophila IFM myosin are modeled on scallop muscle myosin II in the pre-power stroke state (PDB 1QVI) in the presence of the Mg.ADP complex. Functional domains of interest are highlighted: P-loop (blue), switch I (black), switch II (magenta), and Mg.ADP complex (orange, red). F437 and A234 are near to switch I, which is critical for communicating the nucleotide state to the actin-binding site. c Map of the Mhc transgene, which contains transcriptional enhancers located in the 5′ upstream region and first intron [31], along with the entire genomic sequence through the 3′ end of the gene. Translation start (AUG) and termination (TAA) sites are shown as well as the locations encoding the DA residues and key protein regions