Can you imagine that what happens in your heart muscle and maintains your heart beating is a dance-like process with regular rhythms and that any disturbance to this dance may cause serious health problems? It's true. It's a real process that happens at a molecular scale. In a project that spanned seven years at the University of Washington, researchers have managed to detect this mechanism that could someday lead to improved diagnostics and medical treatments for serious and sometimes devastating hereditary heart conditions.
According to a recent study published in the Plos Biology journal, the elements of this biological dance are filament-like proteins in heart muscle cells, named actin, the most abundant protein in the human body. Tropomysin, another protein, wraps itself around the actin filaments.
At the end of the actin filaments, Tropomyosin, together with two other proteins, tropomodulin and leiomodin, act as a sort of cap. But, if that protein makes a mistake and puts the cap on too early, another protein, leiomodin, comes along and knocks the cap out of the way.
"This little dance at the molecular scale might sound insignificant, but it plays a critical role in the development of a healthy heart and other muscles. Mutations in these proteins are found in patients with myopathy," said Alla Kostyukova from the Gene and Linda Voiland School of Chemical Engineering and Bioengineering at the University of Washington, in a report published October 14 on the university's website. According to the findings, one of these conditions, cardiomyopathy, affects as many as one in 500 people around the world and can often be fatal or have lifetime health consequences.
Dmitri Tolkatchev, research assistant professor in the Voiland School and lead author on the paper, said: "This is the first time that this has been shown with the atomic-level precision." The researchers used state-of-the-art approaches to make the key proteins and study them at the molecular and cellular level. The work entailed designing the molecules, constructing them at the gene level in a plasmid (hereditary factors from DNA molecules), and then producing them into bacterial or cardiac cells.
The researchers used nuclear magnetic resonance, which works on the same physical principle as Magnetic Resonance Imaging (MRIs), to understand the proteins' binding at the atomic level.