The details of their model permitted the researchers to explain how, in relaxed muscle, the heads of each myosin molecule are inhibited from interacting with actin by interacting with each other instead. When muscle is activated, they suggest, the bonds between the myosin heads are broken. This frees each head to interact with actin and cause muscle contraction.
"We have focused on the relaxed muscle to understand the structure of the thick filaments when they are not involved in contraction, but rather fully ordered--a state more amenable to understanding their structure," Padron said. "Solving the structure of the relaxed state will allow us to investigate how these filaments are activated when they are switched on."
The scientists were surprised to find that the atomic structure of isolated myosin molecules from vertebrate smooth muscle--the type of muscle found in the digestive tract, bladder, arteries, and veins--closely matched their invertebrate striated muscle myosin filament. Kenneth Taylor's research group at Florida State University reported the atomic structure of the smooth muscle myosin molecules.
The similarity suggests, Padron said, that the interacting head structure may be common to relaxed-state myosin for smooth and striated muscle and among varied species. "This model is applicable across the whole animal kingdom and all muscle types, and that's exciting," he remarked.
Padron said he hopes to apply the research to muscle diseases that arise from malfunctioning of the muscles' on/off switches. One such disease is hypertrophic cardiomyopathy, in which the wall of the left ventricle of the heart becomes enlarged, causing sudden death. It is caused by mutations in certain genes that encode several muscle proteins--some of which are related specifically to the myosin that Padron studies.