Investigating How Inter-domain Interactions Influence The Protein Folding Process

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In the early 1960s, Anfinsen laid down the foundations of the dogma that has become the cornerstone of protein biochemistry: namely, that the native fold of a protein is determined by its amino acid sequence. However, this neglects the role that inter-domain interactions play in the folding of multi-domain proteins. Protein domains by definition are capable of folding into their functional folds independently, but the presence of neighboring domains must also affect the protein fold. The major aim of my research program is to provide a quantitative molecular-level description of: a) how inter-domain interactions contribute to the overall stability of multi-domain proteins; b) how these inter-domain interactions influence the protein folding mechanism. I propose to investigate the significance of these interactions by studying the folding of the enzyme Otu1 from the yeast