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Massry Prize Winners Discuss Protein Folding

Massry Prize Winners Discuss Protein Folding
F. Ulrich Hartl of the Max Planck Institute of Biochemistry

Correct folding of proteins can make the difference between health and disease, according to researchers F. Ulrich Hartl of the Max Planck Institute of Biochemistry and Arthur Horwich of Yale University. The two were jointly awarded the 2011 Massry Prize this month for their work in discovering how proteins fold.

The Meira and Shaul G. Massry Foundation, founded by Shaul G. Massry, professor emeritus of medicine, and physiology and biophysics at the Keck School of Medicine of USC, established the Massry Prize in 1996 to recognize outstanding contributions to the biomedical sciences and the advancement of health. The prize includes a substantial honorarium, and nine of its recipients have gone on to receive the Nobel Prize.

Hartl and Horwich presented details of their research at the 2011 Massry Prize Laureates’ Lectures on Oct. 13. A crowd of Keck School students, faculty and researchers gathered at Aresty Auditorium on the Health Sciences campus to hear the speakers present their research, which spans more than 20 years.

Proteins are made of long chains of amino acids. The chains fold to form specific shapes that help the proteins carry out their specific functions. Improperly or incompletely folded proteins can lead to organ malfunction and neurodegenerative diseases.

During his lecture, Hartl gave some history of his collaboration with Horwich, beginning with their work in 1988 that showed the basic role of chaperone molecules in protein folding. He described how the chaperonins GroEL and GroES create a safe cage structure that allows single-protein molecules to fold. If the protein is not completely folded, it will be recaptured and processed again until it folds correctly.

Working with Huntington’s disease proteins, Hartl also found that disease occurs if there are not enough chaperonins to deal with the number of unfolded proteins. Hartl showed that the antibiotic Geldenamycin affected the number of chaperones, helping to inhibit Huntington protein aggregation.

In Horwich’s presentation, he discussed his initial discovery with then-student Ming Cheng of a yeast mutant that was folding newly imported proteins. A molecular machine composed of the chaperonins GroEL and GroES oversaw the folding process.

Horwich described how proteins must unfold to enter cell mitochondria and then refold once inside. The chaperonin GroEL has dual chambers, like two cups sitting back to back, open at the ends. The chambers attract unfolded protein in alternating cycles.

Once a protein enters one GroEL chamber, GroES then fits on top of the full chamber, encapsulating the protein during folding, which occurs in about 10 seconds. The full chamber then releases the folded proteins while the empty chamber attracts an unfolded protein. Transitioning between the two chambers takes approximately one second.

Hartl and Horwich are hopeful that maintaining a balance between chaperones and unfolded proteins will lead to new treatments for neurological disorders.

Elizabeth Fini, vice dean for research at the Keck School, served as host and moderator for the lectures.

Massry Prize Winners Discuss Protein Folding

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