MICDE Seminar: Margaret Cheung, Department of Physics, University of Houston
October 3 @ 4:00 pm - 5:00 pm
Bio: Margaret Cheung is an Associate Professor of Physics at the University of Houston. She graduated from the National Taiwan University with a bachelor’s degree in chemistry and received her Ph.D. in physics from the University of California, San Diego. She carried out theoretical biological physics and bioinformatics research as a Sloan Postdoctoral Fellow at the University of Maryland and started her lab at the University of Houston in 2006. Professor Cheung’s research is in the field of protein folding inside a cell, calmodulin dependent calcium signaling, and quantum efficiency in artificial photosynthetic materials. She is particularly interested in developing coarse-grained models for protein dynamics in crowded systems, creating multiphysics models that bridge dynamics across wide temporal and spatial scales, and designing computational algorithms that effectively integrate novel high-performance resources. These systems can then be applied for understanding of biological function and for developing therapeutic strategies. She is a fellow of the American Physical Society and a Senior Scientist at the Center for Theoretical Biological Physics at Rice University.
Molecular Underpinning of Postsynaptic Calmodulin-dependent Calcium Signaling
Calcium (Ca2+) is exquisitely utilized by a cell for transducing external stimuli through its gradient of extracellular (~1000 μM) and intracellular (~0.1 μM) concentration. A broad spectrum of Ca2+ signals are encoded by protein calmodulin (CaM) through specific binding with various targets regulating CaM-dependent Ca2+ signaling pathways in neurons. I will focus on binding between CaM and two specific targets, Ca2+/CaM-dependent protein kinase II (CaMKII) and neurogranin (Ng), as they antagonistically regulate CaM-dependent Ca2+ signaling pathways in neurons. I will show the impact of bound calmodulin (CaM)-target compound structure on the affinity of calcium (Ca2+) by integrating coarse-grained models and all-atomistic simulations with non-equilibrium physics. We discovered the molecular underpinnings of lowered affinity of Ca2+ for CaM in the presence of Ng by showing that the N-terminal acidic region of Ng peptide pries open the β-sheet structure between the Ca2+ binding loops particularly at C-domain of CaM, enabling Ca2+ release. In contrast, CaMKII peptide increases Ca2+ affinity for the C-domain of CaM by stabilizing the two Ca2+ binding loops. Through distinctive structural differences in the bound complexes of apoCaM-Ng13-49 and holoCaM-CaMKII, CaM’s affinity for Ca2+ is delineated by its progressive mechanism of target binding. I will discuss them in the context of evolution and in the crowded environment.
Prof. Cheung is being hosted by Prof. Geva (Chemistry)