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 protein capsids of many viruses respond dynamically to environmental signals such as DNA or RNA packaging, receptor binding, and changes in pH or ionic composition. As a result, they undergo conformational changes that involve the concerted reorganization of hundreds of protein subunits and nucleic acid. Small-angle x-ray scattering (SAXS) is ideally suited to monitoring these structural changes in solution. We propose to use SAXS to monitor the dynamic conformational changes observed in two types of icosahedral virus particles, 1) an empty phage head capsid composed of 420 identical subunits (HK97 bacteriophage) and 2) a ssRNA insect virus composed of 240 identical capsid proteins and encapsidated RNA (N-omega-V tetravirus). The data we obtain will be used for generating low-resolution 3D reconstructions as well as for quantitative analysis of time-resolved structural changes using Singular Value Decomposition (SVD). The primary intellectual goals of the proposed studies are to measure the extent of cooperativity among subunits during large-scale conformational changes of these massive and complex assemblies, and to probe for the existence of kinetic and equilibrium intermediate states. By quantitatively addressing these issues we hope to better understand virus function and to enlighten future strategies for targeting capsids with antiviral compounds and neutralizing antibodies.
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