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Signal Transduction by EF-hand Calcium-Binding Proteins.

Calcium and calcium-binding proteins (CaBPs) play a central role in intracellular signal transduction pathways and are associated with a wide-range of effects on health and disease. Our research is directed towards understanding the molecular basis for the cellular activities of CaBPs, particularly the transduction of calcium signals. Ultimately, we seek the ability to control binding properties and interactions with target proteins, thereby enabling the design of specific biological activities and therapeutic strategies relevant to CaBP-mediated disease. The primary experimental approach involves the determination of the three-dimensional structures and internal dynamics of specific CaBPs in the presence and absence of calcium and cellular targets, using NMR spectroscopy in combination with computational methods. These are complemented by comparative structural analysis and protein engineering experiments. The results enable a detailed evaluation of the consequences of binding on the protein's structure and dynamics, provide insights into the energetics of binding, and are used to elucidate the fundamental principles that govern the Calcium-induced activation of CaBPs and the regulation of corresponding biochemical pathways.

Current Projects:

1. Creation of a new hybrid Calcium-binding protein, calbindomodulin, that converts the signal modulator calbindin into a calmodulin-like Calcium sensor.
2. Characterization of the role of caltractin in centrosome duplication.
3. Elucidation of the importance of binding-induced changes in protein dynamics in fine-tuning Calcium-binding protein function.
4. Understand the role of Zinc in modulating the functional properties of S100 proteins.
5. Define the molecular basis for binding of arachadonic acid by the inflammation-associated proteins S100A8 and S100A9.
6. Determine if there exists a common mechanism for calcium-dependent regulation of cytoskeleton remodeling and kinase activity by S100 proteins.
7. S100-mediated regulation of specific [not ready to release details] receptors .

Signal Transduction by EF-hand Calcium-Binding Proteins | DNA Replication Recombination and Repair