A Yale researcher has discovered that it is not necessary to have a greasy core in order to fold a protein, which is a whole new way of looking at these critical molecules.
Protein folds within each cell are of great interest to researchers, particularly medical researchers, because alternatively folded proteins are known to be a factor in diseases such as adult-onset diabetes and Alzheimer’s.
“Protein folding is now a major subject in biochemistry and biophysics that has many ramifications for normal cells and for disease,” said Donald Engelman, the Eugene Higgins Professor of Molecular Biophysics and Biochemistry at Yale, whose study is published in the Jan. 27 issue of Nature magazine. “In some diseases it appears proteins that don’t fold correctly are involved.”
Until now, it was thought that proteins organized themselves in one way: the proteins first form the long stringy polypeptide, then collapse to a compact shape by separating their oily parts from water, and then organize themselves to make detailed functional structures.
What is new here is the concept that a protein can organize itself differently, without the use of this hydrophobic, collapsed mechanism.
Engelman’s collaborator was Shohei Koide of the University of Rochester Medical Center.
Engelman and his co-investigator studied and modified the structure of a protein that has a region that does not seem to have what was believed to be the essential hydrophobic core. “So, there is at least one alternative way of folding a protein without this feature that everyone thought was the key,” Engleman said. “This is a paradigm shift.”
