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- Lab Overview
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- Muscle Assembly Group
- Muscle Physiology Section
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Muscle Physiology Section
Leepo Yu, Ph.D.
Section Leader, Muscle Physiology Section
Phone: (301) 496-5880
Fax: (301) 480-0798
E-mail: yule@mail.nih.gov
Research Overview
The long term goal of our research is to understand the molecular processes underlying muscle contraction. Muscle contraction is a result of interactions between the proteins, myosin and actin by using adenosine triphosphate (ATP) as the energy source. The mechanism of transforming the energy stored in the molecule ATP (chemical energy) to mechanical energy (moving objects) has been a subject of intense research for many years. The reason for such strong interest is that most of the motile processes in living cells such as cell division and nutrient transport, appear to follow similar principles as those found in muscle contraction. The knowledge gained from studying muscle contraction thus far has benefited research work in many other dynamic cellular functions. We focus on the study of changes in actin and myosin that enable the muscle to produce force and to move objects. Although the sliding filament model of muscle contraction is well accepted, the structural details of the mechanism have proved to be difficult to establish because the underlying processes are rapid (millisecond time scale) and the interactions are not synchronized. However, it is known that as the myosin molecule (acting as an enzyme) hydrolyses ATP, it passes through several intermediate states. One way to study the structural details is to study structures of each individual state within the ATPase cycle. For this purpose, we have been using ATP analogues that trap the myosin molecules in individual intermediate states. X-ray diffraction is the technique of choice, since it is one of the few non-invasive techniques that allow direct observation of molecular structures in living muscle cells.
The diffraction patterns (fiber diffraction) reveal how the myosin heads (the enzymatic part of the molecule) are distributed along the myosin filaments and how they interact with actin in the actin filament in muscle. Most of the experiments are carried out by using the intense x-ray sources at the National Synchrotron Light Source at the Brookhaven National Laboratory, New York.
Recent findings include characterizing several well-defined structures of actin and myosin filaments as they go through their cycles of operation associated with ATP hydrolysis.
Selected Publications
Xu S, Offer G, Gu J, White HD, Yu LC. Temperature and ligand dependence of conformation and helical order in Myosin filaments. Biochemistry. 2003; 42(2):390-401.
Gu J, Xu S, Yu LC. A Model of Cross-Bridge Attachment to Actin in the Actin-Myosin-ATP State Based on X-Ray Diffraction from Permeabilized Rabbit Psoas Muscle. Biophysical J. 2002; 82: 2123-33.
She M, Trimble D, Yu LC, Chalovich JM. Factors contributing to troponin exchange in myofibrils and in solution. J Muscle Res Cell Mot. 2000; 21: 737-745.
Kraft T, Xu S, Brenner B, Yu LC. The effect of thin filament activation on the attachment of weak binding cross-bridges: a 2D-X-ray diffraction study on single muscle fibers. Biophys J. 1999; 76: 1494-513.
Frisbie SM, Reedy MC, Yu LC, Brenner B, Chalovich JM, Kraft T. Sarcomeric binding pattern of exogenously added intact caldesmon and its C-terminal 20Kda fragment in skinned fibers of skeletal muscle. J Muscle Res Cell Mot. 1999; 20: 291-303.
See complete list of publications
Updated September 17, 2007
