The functions of the Hsp70 system

Published on October 1, 2007 Updated on May 16, 2020   35 min

Other Talks in the Category: Cell Biology

0:00
My name is Jeffrey Brodsky, I'm a professor at the University of Pittsburgh. Before I embark on this formidable topic, there are several things I need to point out. First, this is a broad topic and therefore it's important to start with some basic paradigms that drive our understanding of how molecular chaperones function in cells and how certain human diseases arise, either from defects in molecular chaperones, or how chaperones impact the ability of certain human diseases to evolve over time in patients with those diseases. I'd like to begin with a certain myth that I think is commonly held in the field of biological sciences.
0:40
The myth is that proteins can fold on their own. In other words, all the information required for protein folding is contained within the primary amino acid sequence of that protein or polypeptide. This myth is actually true when experiments are performed in vitro, because classic studies from Anfinsen and colleagues showed that unfolded or denatured polypeptides in the test tube could refold on their own, assuming that the conditions had been optimized in that in vitro reaction.
1:13
In truth, the cell is a brutal place for a protein to fold, the cell has not necessarily been optimized to engineer or to allow efficient protein folding to take place, and the reasons for this are as follows. First of all, there's a very high concentration of proteins in the cytoplasm of cells, which by and large represents the major compartment in which protein folding occurs. Second, the cell is exposed to various stresses and these stress conditions can compromise the ability of proteins to fold efficiently. Stresses include heat, oxidizing damage, denaturants and other chemical insults such as heavy metals, that reduce protein folding efficiency. In addition, there are spontaneous and inherited mutations in polypeptides that can arise, and this can significantly reduce the efficiency of protein folding in the cell, something that's not encountered in the test tube.