Project 170584

Many important biological processes are controlled by calcium. For example, the transmission of nerve impulses, control of vision and stimulation allowing the heart to beat can not occur without calcium. Frequently, the role of calcium is to bind to specific calcium-binding proteins in the cell, which in turn interact with other proteins or molecules to trigger a biological function. Two important proteins that fulfill this role are S100B and S100A10. In the past 2 years exciting new developments have shown that these proteins also possess calcium-independent protein interactions that impact critical biological functions. For example, both proteins have been shown to interact with receptor proteins whose dysfunction can lead to neural disorders such as depression or Parkinson's disease. Further, S100A10 has been shown to be a member of a large multiprotein complex required to close lesions in the cell membrane that result from injury. We are determining the three-dimensional shapes and interactions of two S100-receptor complexes to understand how the S100 protein controls delivery of the receptor to the plasma membrane. Details of these structures and interactions may allow synthetic molecules to be designed that stimulate or disrupt the protein-protein interaction and control neurological disease.

using NMR spectroscopy to determine three-dimensional structures of S100-receptor complexes