Research Shows How Actin-Thin Filaments Are Kept at Exact Same Length in Healthy Heart; Uneven Lengths Lead to Disease; Work Enabled by Atomic-Precision NMR Analysis

It might look like a little game at the molecular scale. Filament-like proteins in heart muscle cells have to be exactly the same length so that they can coordinate perfectly to make the heart beat. Another protein determines when the filament is the right size and puts a small cap on it. 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 healthy heart and other muscles. Reporting in an article published online on September 8, 2020 in the journal PLOS Biology, a Washington State University (WSU) research team has proven for the first time how the mechanism works. The article is titled “Leiomodin Creates a Leaky Cap at the Pointed End of Actin-Thin Filaments.” The finding could someday lead to improved diagnostics and medical treatments for serious and sometimes devastating hereditary heart conditions that come about from genetic mutations in the proteins. 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. A similar condition called nemaline myopathy affects skeletal muscles throughout the body with often devastating consequences. "Mutations in these proteins are found in patients with myopathy," said Alla Kostyukova, PhD, Associate Professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering at WSU and leader of the project. "Our work is to prove that these mutations cause these problems and to propose strategies for treatment." Heart muscle is made of tiny thick and thin filaments of proteins.
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