Protein molecules are long, complex strings of amino acids that have many possible ways of folding into a compact shape, yet they somehow fold beautifully in the crowded interior environment of a cell. Folding is guided by the sequence of amino acids in a protein but sometimes this process goes bad when proteins are changed because of mutation or when surfaces that are incompatible with the water environment of the cell cytoplasm become exposed during the folding process. Cells have evolved molecular chaperones, such as GroEL, to help shield such surfaces and to provide a protected environment in which to complete the folding process. The surfaces of this remarkable machinery are very forgiving. They actually utilize metabolic energy (i.e., ATP hydrolysis) to alternate their physical chemistry between hydrophobic states and hydrophilic states, which restarts the folding when it stalls and expels the protein when folding is completed. In the case of GroEL, a molecular chaperone shaped like a test tube, access to the cavity is highly selective and limited to only newly-made proteins or those purposely unfolded to repair damage or mistakes.
The 2012 Shaw Prize in Life Science and Medicine is awarded to Ulrich Hartl, Director, Max Planck Institute of Biochemistry in Martisried, Germany and Arthur Horwich, Professor of Genetics and Investigator of the Howard Hughes Medical Institute, Yale University School of Medicine. Together, these two investigators identified the chaperones and their mechanism of action in the cell powerhouse, the mitochondrion, and in the cell sap, the cytoplasm.