ASSEMBLY, DYNAMICS, AND INFECTIVITY OF VIRUSES USING A MASS SPECTROMETRY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The solution-phase protein motion that is part of a multi-component complex is rarely obvious from the high resolution three-dimensional structure. Protein function is intimately connected to dynamics and therefore knowledge of the frequency, range, and coordination of motion by supramolecular complexes is critical to understanding how they function. Dr. Bothner's lab uses viruses as a paradigm for studying protein dynamics in supramolecular complexes. They have recently made the first measurements of the free energy and equilibrium properties for large scale protein motion within a megadalton complex. Systems currently under investigation include Hepatitis B, Norwalk, and Canine Parvovirus. Dr. Bothner's work has demonstrated that protein dynamics are an inherent feature of virus particles. In each case, the identified protein domains correlate with domains that play important roles in infection. Viruses are obligate cellular pathogens and therefore many cellular proteins are critical for viral infection, replication, and release from a host cell. Using proteomics-based approaches, we are seeking to identify cellular proteins that are hijacked by viruses during the infection process. The significance of this work is two fold; the basic biology of viruses can be elucidated and novel targets for antiviral agents will be identified.