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SAXS STUDIES ON PROTEIN-NUCLEIC ACID COMPLEXES

$6,487P41FY2009RRNIH

Illinois Institute Of Technology, Chicago IL

Investigators

Linked publications & trials

Abstract

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 first project is to study the role of conformational transitions in the viral sensor protein RIG-I in viral infection. Many human cells are capable of sensing viral infection and mounting an innate immune response1. How this antiviral immune response is triggered has been a central question in the fields of virology and human immunology. The clearest answer to this puzzle has come recently with the discovery of retinoic acid inducible gene-I (RIG-I) like proteins as the primary sensors of invading viruses, leading to the production of type I interferons (IFN-[unreadable]/[unreadable]) and other antiviral proteins. An unresolved question is how RIG-I recognizes and responds to virus infection. The current model for RIG-I is that it exists in a "closed" conformation in uninfected cells, but upon viral infection and association with virus-specific RNAs (and ATP) it changes to an "open" conformation, allowing interaction with downstream signaling proteins. SAXS studie sare proposed to test this hypothetical model. The second project studies the ATP-dependent molecular motor: EcoP15I, a Type III restriction enzyme that moves on the DNA. Along with enzymes such as helicases and polymerases, they convert chemical energy into mechanical energy for work on the DNA. Although, type III restriction enzymes have been studied biochemically and genetically for >35 years, there is still no structural information on these fascinating ATP dependent motors. SAXS analysis of the complex will provide an independent assessment of its size and shape that may be compared to our preliminary EM analysis.

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