Investigating a protein involved in cardiomyopathy

Unravelling the mystery of the hierarchical phosphorylation of MyBP-C and its importance for differential interactions with actin and myosin

Dr Mark Pfuhl is studying heart muscle proteins that help the heart to beat properly and maintain its structure. He wants to work out what goes wrong with these proteins in people with hypertrophic cardiomyopathy, a condition that affects heart muscle. Genetic changes in a protein called myosin binding protein C (MyBP-C) are one of the most common causes of hypertrophic cardiomyopathy, when the heart becomes enlarged and cannot pump as effectively as it should. MyBP-C can also be faulty in dilated cardiomyopathy. The MyBP-C protein appears to be controlled by a chemical change called phosphorylation, and this happens less frequently in heart failure. In this project, Dr Pfuhl will study the MyBP-C protein in minute detail to better understand the role of phosphorylation in its biology and how it is linked to heart disease. He will work out the three dimensional structure of a portion of the MyBP-C protein and how it interacts with other proteins. He is trying to understand how the structure changes when it is phosphorylated, and how phosphorylation controls how MyBP-C interacts with two other key muscle proteins called actin and myosin. Dr Pfuhl’s work could help us better understand how genetic changes in MyBP-C lead to hypertrophic cardiomyopathy and could reveal new ways to treat the condition.