A new twist on protein folding
As disordered, one-dimensional strings of amino acids, proteins cannot carry out their essential work in cells. In order to function, these complex molecules must first fold into stable, three-dimensional structures.
It has long been assumed that proteins must have an oily core to reach a stable configuration. But Donald M. Engelman, Ph.D., professor of molecular biophysics and biochemistry, and Shoei Koide, Ph.D., a collaborator at the University of Rochester Medical Center, have shown that the process can indeed vary. Their findings represent a major shift in the previously standard view of protein folding.
Protein folding is a subject of intense scientific interest, because incorrect folding is a factor in chronic diseases including adult-onset diabetes and Alzheimer’s disease. Medical researchers hope to understand protein folding not only to develop diagnostic tools and therapies for diseases caused by failure of the process, but to understand the information in the genome.
Previously it was believed that proteins organize themselves by first forming a long, stringy polypeptide that then collapses into a compact shape by separating its oily parts from water. At that point, the proteins organize themselves into functional structures. In an article that appeared in the January 27 issue of Nature, the two scientists reported that they had modified a protein in such a way that it organized itself without use of the hydrophobic, collapsing mechanism. “There is at least one alternative way of folding a protein without this feature that everyone thought was the key,” said Engelman. “This is a paradigm shift.”