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Protein Nanomaterials as Tools for Cryo-EM Structural Analysis

Abstract

In the last few decades there has been tremendous technological and computational advances in the field of cryo-electron microscopy which has led to a phenomena referred to as “The Resolution Revolution,” in which the number of high resolution structures solved via this technique has exploded. Despite these advances, there still remains a size limitation for your target of interest, below which high resolution microscopy remains challenging. Adding to this, a vast majority of the biologically relevant proteins and nucleic acids inside of cells lie below this size limit. Parallel advances in protein design may provide an avenue for progress on this challenging problem. By designing large protein assemblies, we are able to artificially increase the size of a given target, making it amenable to cryo-EM studies. This thesis describes recent advances in the field as well as efforts to generate imaging scaffolds for both small cancer-related protein targets, and RNA molecules. The knowledge gained through these endeavors will better guide future design efforts.

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