SOLUTION SCATTERING IN THE STUDY OF POLYPROTEIN STRUCTURE IN INFECTIOUS DISEASES

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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. Emerging infectious diseases continue to be a major threat to public health. Antibiotic resistant bacteria and rapidly mutating viruses are always driving the search for new antibiotic and antiviral targets. Multi-functional multi-domain polyproteins are an essential and underrepresented class of targets, largely due to a lack of structural and functional characterization of these large proteins. We present preliminary results using the technique of small angle x-ray scattering (SAXS) that demonstrate the feasibility of structural studies on polyproteins. We have used a method of overlapping constructs to verify the structures of polyprotein intermediates from the SARS coronavirus. We have also produced SAXS reconstructions of a non-ribosomal peptide synthetase used by pathogenic bacteria to scavenge iron during an infection. The techniques developed by this research will be applicable to a wide range of viruses and bacteria.