"Press Release" - the story behind the research

Luther, P. K., H. Winkler, et al. (2011). "Direct visualisation of myosin binding protein C bridging myosin and actin filaments in intact muscle." Proc Natl Acad Sci U S A: doi/10.1073/pnas.1103216108.

            A protein in the muscle of our heart called myosin binding protein C (MyBP-C) has gained great importance since the discovery fifteen years ago that mutations in this protein lead to heart disease resulting in enlarged hearts.  This is a relatively common disease affecting 1 in 500 but in some countries like India, one particular mutation affects 4% of the population.  This condition is also the most common cause of death in young athletes on the field.  Although the protein was discovered nearly 40 years ago we do not know its role or its arrangement in heart muscle.  Experiments in which it is extracted show that MyBP-C may speed up or slow down the contraction by binding to the protein filaments in muscle.  These filaments, myosin and actin, interact and slide past each other during muscle contraction.  But these earlier studies were on  isolated proteins; the truth about MyBP-C action can only be found by studying them in their correct environment in the heart.  A very similar protein occurs in our skeletal muscles (those that move our limbs) and a new paper in PNAS reports on a multinational collaboration to understand the structure of MyBP-C in these muscles.  The story begins in 1988 when Venezuelan researcher Padron got together with Craig in his laboratory at the University of Massachusetts Medical School in Worcester, Massachusetts, to prepare samples of frog muscle for electron microscopy, a technique capable of revealing the molecular details of cell structure.  To preserve muscle fibres in the most life-like fashion, the best method is to freeze them rapidly.  This was achieved by slamming a small bundle of fibres against a highly polished copper block cooled with liquid helium.  This yielded superb pictures when examined in the electron microscope.  MyBP-C occurs on fine but elusive stripes and these pictures have these stripes in abundance.  Researcher Luther based at Imperial College London, specialising in electron tomography (as this field of 3D imaging is called), contacted the pair and a collaboration was started for Luther to examine the samples and by tomography to reveal the arrangement of MyBP-C.  Funded by the British Heart Foundation, Luther conducted preliminary electron microscopy at Imperial College London and then travelled to Florida State University, Tallahassee, Florida, to work in Taylorís laboratory, a leading centre for electron tomography of such samples.  Using Taylorís state of the art electron microscope, Taylorís associate, Liu, and Luther recorded images of the sample and prepared the electron tomograms.  The next crucial step was image processing, and using the pictures of hundreds of muscle filaments in the tomograms, Liu and Luther produced average images of the myosin filament.  This gave the first detailed picture of how MyBP-C is organized on the myosin filament.  Most importantly, it showed directly that MyBP-C forms a link between the myosin and actin filaments, a possibility that had long been suggested but never before demonstrated.  This link may be how MyBP-C influences contraction, by regulating the rate at which myosin and actin filaments can slide past each other.  Now Luther and his team are working to repeat the study for cardiac muscle.