The goals of the research program are to use structural and biochemical methods to investigate the relationship between structure and function of three essential viral proteins, the 3AB protein and its cleaved progeny, the 3A and 3B proteins. The poliovirus 3AB protein is an important, multifunctional protein that plays several critical roles in viral replication in members of the Picornaviridae family. Multidimensional heteronuclear NMR spectroscopy will be used to determine the high-resolution solution structure of the 3A and 3AB proteins from human poliovirus. The fundamental chemical nature of the interactions between 3AB and its biological partner, the viral polymerase, will be probed using biochemical, biophysical and structural methods. Finally, the 3A and 3AB structures will be refined using dipolar couplings obtained by new methods for biomolecular alignment in a magnetic field. Because the 3A and 3AB proteins are found in all picornaviruses, a better understanding of their structures and functions will provide important insights into the fundamental biochemistry of a large number of important viral systems, as well as advance our understanding of how protein/protein interactions modulate biological activity. The aims of the education program are to integrate bioinformatics and biomolecular structure analysis into the undergraduate biochemistry curriculum at the University of Colorado at Boulder. The use of bioinformatics tools, such as sequence comparison, analysis of complete genome sequences, and visualization and manipulation of biomolecular structures are essential components of training in modern biochemistry. The explosion of information and tools available over the Internet, and the number of three-dimensional structures that have become available in the last few years indicate this aspect of biochemistry is only going to increase in impact over time. This project will develop the tools needed to incorporate this powerful new area of biochemistry into the training of biochemistry undergraduate and graduate students in order to prepare them for their future in professional schools and industry.
2 GENERAL ABSTRACT
The goals of the research program are to use structural and biochemical methods to investigate the relationship between structure and function of three essential viral proteins, the 3AB protein and its cleaved progeny, the 3A and 3B proteins. These proteins are produced by an important family of viruses, the picornaviruses, whose members include the causative agents of polio and the common cold. The three-dimensional structure of these proteins will be related to their biological functions. The fundamental chemical nature of the interactions between these proteins and the protein partners they interact with will be probed using biochemical, biophysical and structural methods. Because the 3A and 3AB proteins are found in all picornaviruses, a better understanding of their structures and functions will provide important insights into the fundamental biochemistry of a large number of important viral systems, as well as advance our understanding of how protein/protein interactions modulate biological activity. The aims of the education program are to integrate bioinformatics and biomolecular structure analysis into the undergraduate biochemistry curriculum at the University of Colorado at Boulder. The use of bioinformatics tools, such as sequence comparison, analysis of complete genome sequences, and visualization and manipulation of biomolecular structures are essential components of training in modern biochemistry. The explosion of information and tools available over the Internet, and the number of three-dimensional structures that have become available in the last few years indicate this aspect of biochemistry is only going to increase in impact over time. This project will develop the tools needed to incorporate this powerful new area of biochemistry into the training of biochemistry undergraduate and graduate students in order to prepare them for their future in professional schools and industry.
