Mapping interactions between myosin relay and converter domains that power muscle function

Area of Science:

• Muscle physiology
• Molecular biology
• Biochemistry

Background:

• Intramolecular communication in myosin is crucial for motor function.
• Specific amino acid interactions mediating this communication in muscle cells remain unclear.

Purpose of the Study:

• To investigate the role of specific amino acid residues in the relay loop of skeletal muscle myosin in intramolecular communication.
• To define the importance of residues Ile(508), Asn(509), and Asp(511) in communicating with converter domain residue Arg(759).

Main Methods:

• Utilized a novel in vivo molecular suppression analysis in Drosophila melanogaster skeletal muscle myosin.
• Performed molecular modeling to elucidate the interaction mechanism.

Main Results:

• The N509K relay mutation suppressed defects caused by the R759E converter mutation in myosin ATPase, in vitro motility, myofibril stability, and muscle function.
• The I508K and D511K mutations did not suppress R759E, with I508K impairing motor function and myofibril assembly.
• A mechanism for the relay-converter interaction was defined.

Conclusions:

• The interaction between myosin residues 509 (Asn) and 759 (Arg) is critical for skeletal muscle myosin's biochemical and biophysical functions.
• This interaction is essential for normal muscle ultrastructure, mechanical properties, motor function, and myofibril assembly.