Chaperonin-mediated protein folding 2

Published on September 10, 2012   45 min

A selection of talks on Biochemistry

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I'm going to review how folding occurs in an encapsulated chamber and I'll discuss how the nucleotide cycle is used to drive the GroEL and GroES chaperonin and machine forward through its reaction cycle. Finally, I'll present a summarizing movie that essentially connects all the dots of X-ray structures and EM structural information to give us a working, coherent picture of how the reaction cycle works.
Now, I want to talk about the folding reaction mediated by the GroEL/GroES system, and here, ongoing collaborations with Helen Saibil have been critical to our understanding of this system.
When we initially looked at one of our favorite substrates, rhodanese taking the model for its native state and imposing on the apical domains of GroEL, while associated with GroEL. We noticed that there's a terrible steric clash between rhodanese and the apical domains. This suggested that there was no way that rhodanese could productively reach the native state inside of unliganded GroEL. But, Helen changed our thinking about how folding could occur.
What she observed was that when GroES binds to GroEL, the side of GroEL to which GroES associates opens up, that is the apical domains open up and a chamber is produced in which one could envision that potentially a polypeptide could fold. By contrast, if you look at the opposite ring, which is not bound by GroES, it occupies a relatively closed state, which is consistent with the 45 Angstrom diameter open ring. Here on the GroES-bound side, things have opened up considerably.