Tuesday Oct. 16, 2012
Gil Alterovitz (Harvard, MIT)
Signal processing is critical in both engineering and biological systems. In biomolecular systems, signal transduction pathways via protein interactions are of critical importance in disease and regulation of cellular functions. Just like reconfigurable chips/networks in engineering, biomolecular systems are emerging with similar properties.
Proteins that do not fold to a state of stable, ordered 3-D structure (i.e. disordered proteins) are highly represented in signaling pathways and protein interaction networks that communicate and process information. Specific regions within these disordered proteins, however, can take on an ordered structure upon binding to a partner. While predicting disordered regions and interacting segments within these regions can be done with fair accuracy, the nature of the resulting protein-protein interactions has not been established. Here, we show that these reconfigurable Order-Disorder Interfaces (ODIs) are more critical in diseases than the order-order interfaces interactions commonly considered to be the major players in signaling. Via large-scale analysis, we also show that reconfigurable interfaces play novel, significant roles in disease and development drug resistance- with applications in engineering of new, more flexible biomolecular signaling mechanisms. Insights from the biomolecular world can be translated to development of new types of engineered systems as well.
Center for Biomedical Informatics, Harvard Medical School, Boston, MA.
Children’s Hospital Informatics Program at Harvard-MIT Division of Health Science, Boston, MA.
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA.