MOLECULAR MECHANISMS OF CALCIUM-DEPENDENT CELL REGULATION
Calcium plays an essential role as a structural element and as a second messenger in the regulation of an array of cellular processes. However, the calcium ion itself encodes no intrinsic information. The cellular signal represented by fluctuations in calcium ion concentrations must be interpreted by specific calcium-binding proteins which act to regulate the activity of other enzymes or proteins. The importance of proteins that bind calcium is underscored by the lethality of disrupting these genes in transgenic mice, and genetic diseases which result from mutations in genes that encode calcium binding proteins. Thus, an understanding of structure/function relationships in calcium binding proteins would provide unique insights into the structural basis of diseases, and provide a data base of information for the development of drugs that can alter the properties of regulatory calcium binding proteins.
My laboratory applies a synergistic blend of molecular and structural biology to study the molecular anatomy of calcium binding proteins. Current projects focus on cardiac troponin C, calmodulin, and cartilage oligomeric matrix protein (COMP). Areas of interest include: The mechanisms of regulation of calmodulin activity by post-translational modification and modulation of calmodulin binding to target proteins; Exploring the molecular mechanism of regulation of cardiac muscle contraction by calcium binding to cardiac troponin C, and how cardio-tonic drugs lead to an increased efficiency of cardiac muscle contraction; Using NMR to reveal the structural basis behind why mutations in the extracellular matrix protein COMP lead to skeletal dysplasia and dwarfing syndromes.
Contraction and relaxation of the human heart depends on the binding and release of calcium from cardiac troponin C.
The figure above shows the NMR solution structure of this critical regulatory protein
UTHealth Medical School
Department of Biochemistry and Molecular Biology
6431 Fannin Street, MSB 6.106
Houston, Texas 77030
713-500-6061 Direct 713-500-0652 Fax
Ph.D. - University of California, Riverside
Postdoctoral Fellow - Baylor College of Medicine
Structural and molecular basis of calcium signaling in normal and disease states
Biochemistry. 2010 Dec 7;49(48):10287-97. doi: 10.1021/bi100500m. Epub 2010 Nov 12.
PMCID: PMC3001392read more