Protein folding and assembly

One of the central dogmas in biochemistry is the view that the biologically active, three-dimensional structure of a protein is unique and exclusively determined by its amino acid sequence, and that the active conformation of a protein represents its state of lowest free energy in aqueous solution. Despite a large number of novel experiments supporting this view, including an exponentially increasing number of solved three-dimensional protein str uctures, it is still impossible to predict the tertiary structure of a prot ein from knowledge of its amino acid sequence alone. Towards the goal of identifying general principles underlying the mechanism of protein folding in vitro and in vivo, we are pursuing several projects that are briefly described in this article: (1) Circular permutation of pro teins as a tool to study protein folding, (2) Catalysis of disulfide bond f ormation during protein folding, (3) Assembly of adhesive type 1 pili from Escherichia coil strains, and (4) Structure and folding of the mammalian pr ion protein.