The proteins in our cells are produced as long chains of amino acids that must fold precisely into their final shape. The key players in this folding process are the so-called molecular chaperones; protein helpers that make sure this process is successful. Researchers from Utrecht University, in close collaboration with colleagues from Heidelberg University, have at last uncovered how the two most important chaperone families, Hsp70 and Hsp90, cooperate in this folding process. Surprisingly, it turns out they do not actively assist in the folding, as scientists had long assumed. Instead, they simply prepare the proteins for spontaneous, productive folding. This breakthrough in understanding the functioning of the Hsp70-Hsp90 cascade was published only by Molecular Cell on 3 May.
Incorrectly folded proteins can result in serious diseases, such as Cystic Fibrosis and many neurodegenerative diseases like Alzheimer’s. Scientists have long known that Hsp70 and Hsp90 play a key role in this folding process, and that Hsp90 acts downstream of Hsp70. However, the actual mechanism by which they fold a protein has remained enigmatic.
PhD candidate Tania Morán Luengo from Utrecht University has recently demonstrated that the chaperone Hsp70 binds to the young protein, protecting it while also preventing it from folding. Then Hsp90 breaks the Hsp70 block, which allows the protein to continue folding into the correct state all by itself. This discovery signalled the surprising end of the longstanding belief that chaperones fold proteins. For her outstanding work, Morán Luengo was selected as Bijvoet Center PhD Student of the Year.