Abstract
The molecular motor, myosin, generates force and movement on actin filaments. High-resolution structures have provided insights into how the hydrolysis of adenosine triphosphate (ATP) and subsequent release of the hydrolysis products lead to movement on actin. The small structural changes within the motor itself are amplified into large movements by a region known as the myosin lever arm. How myosin interacts with actin to generate force is a subject of considerable controversy. The major debate centers on understanding at what point in force generation the inorganic phosphate is released with respect to the lever arm swing or powerstroke. Resolving the controversy is essential for understanding how force is produced as well as the mechanisms underlying disease-causing mutations in myosin. Recent structural insights on the powerstroke have come from high-resolution structure of myosin in a previously unseen state and from an electron cryo-microscopy (cryo-EM) 3D reconstruction of the actin-myosin-MgADP complex. Seemingly contradictory data from time-resolved Fluorescence Resonance Energy Transfer (FRET) studies can be reconciled and a model for myosin force generation on actin emerges from these data.
About the speaker
Prof H Lee Sweeney received his Bachelor’s degree in Biology and Biochemistry from Massachusetts Institute of Technology, MA in Physiology and PhD in Physiology and Biophysics at Harvard University. He then started his early academic career at University of Texas at Austin from 1985 to 1989. After that, he joined University of Pennsylvania School of Medicine, where he rose from Assistant Professor of Physiology to Professor of Physiology, Medicine and Surgery. He has moved to University of Florida as the Thomas H Maren Eminent Scholar Chair Professor in the Department of Pharmacology and Therapeutics since 2015.
Prof Sweeney is one of the most famous and established scientists in the area of molecular motor of the myosin superfamily. He is also an expert in the therapy for muscle disease. Until now, he has published more than 200 journal papers and more than 28000 citations with h-index of 74. He served at the editorial boards for a number of academic journals, as member for American Journal of Physiology (Cell Physiology) (1991-1994), as consulting editor for Journal of Applied Physiology (1999-2002) and as member for The Journal of General Physiology (2001-2006).
Prof Sweeney’s research is well recognized by numerous honors, including Stanley N. Cohen Biomedical Research Award (2010), Hamdan Award for Medical Research Excellence (2008) and the Established Investigator of the American Heart Association (1990-1995). He was elected as fellows of the Biophysical Society (since 2017) and the American Heart Association (since 2001).
|
