Novel regulatory mechanisms and structural aspects of oxidative protein folding

The basic unit of life, the cell, utilizes a great variety of molecules to sustain life. One such important molecule, with thousands of different types found in human cells, is protein. Proteins act in various biological roles, including formation of cellular structures, signaling within and between cells, as well as in immune system to protect against extracellular threats. Protein resembles beads on a string: it first forms a linear sequence of consecutive amino acid residues. To acquire biological function, protein must fold. During folding, amino acid residues start reacting with each other, and the linear chain compacts into a three-dimensional, often globular structure. In my doctoral research, I have studied chemical reactions of a specific amino acid, cysteine, which is involved in protein folding. Two cysteines can form a disulfide bond which stabilizes protein structure and may regulate the biological function of a protein. Together, disulfide formation and protein folding form a complex catalyzed process which must be aided by various cellular protein folding factors, including enzymes. I analyze the mechanism of action and interactions between such folding factors and their regulation to understand better, how cells form disulfides, fold proteins efficiently, and avoid folding mistakes. Industrial production of many important disulfide-containing proteins, including insulin and antibodies, is currently complicated and expensive due to the complexities connected to protein folding and disulfide bond formation. I hope that the results from this work will help solve those problems in the future.