IA. Chaperone-Assisted Protein Folding
IB. Chaperone-Assisted Protein Folding
II. The Role of ATP Binding and Hydrolysis at GroEL
III. Where are Proteins Folded by Chaperonins?
Part IA: Chaperone-assisted protein folding
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Horwich begins with a brief history of the discovery of the chaperonins and their importance in proper protein folding. He then gives an overview of two well-studied families of chaperones, heat shock protein 60 (Hsp60) and Hsp70.
In Part 1 B, Horwich continues with a review of the Calnexin, Hsp90 and small Hsp families. He discusses how transcriptional regulation in response to chemical or heat stress results in an increase in effector chaperonins. Finally, Horwich poses the question of why chaperonins are not effective in preventing protein aggregation or misfolding in a number of devastating neuronal diseases.
Horwich discusses experiments designed to decipher how chaperones mediate protein folding in Part 2 of his talk. He describes in detail the role of ATP binding and hydrolysis by the GroEL/GroES complex in promoting correct protein folding.
In Part 3, Horwich describes the experiments that determined that proteins are, in fact, folded within the chaperonin complex and exactly where folding occurs.
Arthur Horwich received his AB and MD from Brown University. Following a pediatric residency at Yale, Horwich did two postdoctoral fellowships, first with Tony Hunter and Walter Eckhart at the Salk Institute and second with Leon Rosenberg at Yale, before joining the Yale faculty.
Currently, Horwich is Sterling Professor of Genetics and Pediatrics at Yale School of Medicine and an Investigator of the Howard Hughes Medical Institute. He is interested in understanding how chaperonins promote the correct folding of proteins in the cell. More recently, Horwich has focused his efforts on understanding the consequences of protein misfolding, particularly in ALS or Lou Gehrig’s disease.
Horwich is a member of the National Academy of Sciences and has received numerous awards for his work including the Gairdner International Award. Together with his long time collaborator Franz-Ulrich Hartl, Horwich has been awarded the Wiley Prize, the Louisa Gross Horwitz Prize and the Albert Lasker Award for Basic Medical Research, among other prizes.
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