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- New Study Focuses on the Mechanism of Cardiac Contraction, to better understand the role of myosins
The contraction of the heart muscle is a highly regulated process. It is made possible by proteins called myosins. Mutations in these proteins can lead to heart failure. Combining structural studies with molecular dynamics simulations, a new study conducted at Institut Curie provides a better understanding of how the different states of myosin are regulated. These findings, published in Nature Communications on June 4, 2026, pave the way for more personalized medicine for patients with cardiomyopathies.
Myosins are proteins essential for heart contraction. Several mutations in these proteins can lead to cardiomyopathies, which, over the long term, can result in heart failure.
The Structural Motility team led by Dr. Anne Houdusse, a CNRS Research Director in the Cell Biology and Cancer unit (CNRS UMR144 / Sorbonne University), is studying the mechanisms that regulate cardiac contraction. Understanding these mechanisms could lead to the development of treatments for cardiomyopathies.
Fine-Tuning of Cardiac Activity
“In the heart, only certain myosins are active and participate in contraction. The others are kept in an inactive regulatory state known as the sequestered state. This allows the number of active proteins to be adjusted as needed—for example, during physical activity,” explains Dr. Julien Robert-Paganin, a CNRS research fellow in Anne Houdusse’s team and co-last author of this new study published in Nature Communications.
The team resolved this self-inhibited state of myosins in 2023. “This was a major breakthrough in our understanding of heart disease. However, fundamental questions remain, particularly regarding the recruitment of myosins in their sequestered state. To observe the dynamic states of this myosin at high resolution, we used new methodologies,” adds Julien Robert-Paganin.
The Dynamics of the Self-Inhibited State
The researchers combined cryo-electron microscopy1 and the study of molecular dynamics. "These complementary approaches have shown that a mutation does not alter the structure but rather the ability to explore various dynamic states. Our study has enabled us to reconstruct a model of how these motors assemble within cardiac cells, allowing us to better understand the factors that stabilize their resting state. This makes it possible to predict how other mutations might also disrupt cardiac contractility,” continues Anne Houdusse.
Toward More Personalized Medicine
There are hundreds of mutations that cause hereditary cardiomyopathies. “All of these mutations have different molecular effects, but they can all result in abnormal heart contractions, which must be treated differently. The clinical goal behind our research is to develop a panel of molecules tailored to the different mutations, which will allow us to personalize the therapeutic approach for each patient,” concludes Anne Houdusse.
[1] The principle of cryomicroscopy is based on the very rapid freezing of a protein sample at extremely low temperatures. An electron beam is then passed through this sample. The resulting images make it possible to reconstruct and study the three-dimensional structure of proteins.
References : Dynamics of the β-cardiac myosin auto-inhibited state explain cardiomyopathy pathogenesis - Daniel Auguin, Laurie Lannes, Carlos Kikuti, Nour Ayoub, Marie Juillé, Stéphane Réty, Neha Nandwani, Divya Pathak, Kathleen M Ruppel, James A Spudich, Julien Robert-Paganin, Anne Houdusse – Nature Communications - https://doi.org/10.1038/s41467-026-73572-5
