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Extensive Sampling of the Cavity of the GroEL Nanomachine by Protein Substrates Probed by Paramagnetic Relaxation Enhancement.


ABSTRACT: The chaperonin GroEL is a 800 kDa nanomachine comprising two heptameric rings, each of which encloses a large cavity or folding chamber. The GroEL cycle involves ATP-dependent capping of the cavity by the cochaperone GroES to create a nanocage in which a single protein molecule can fold. We investigate how protein substrates sample the cavity prior to encapsulation by GroES using paramagnetic relaxation enhancement to detect transient, sparsely populated interactions between apo GroEL, paramagnetically labeled at several sites within the cavity, and three variants of an SH3 protein domain (the fully native wild type, a triple mutant that exchanges between a folded state and an excited folding intermediate, and a stable folding intermediate mimetic). We show that the substrate not only interacts with the hydrophobic inner rim of GroEL at the mouth of the cavity but also penetrates deep within the cavity, transiently contacting the disordered C-terminal tail, and, in the case of the folding intermediate mimetic, the base as well. Transient interactions with the C-terminal tail may facilitate substrate capture and retention prior to encapsulation.

SUBMITTER: Walti MA 

PROVIDER: S-EPMC6029692 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Extensive Sampling of the Cavity of the GroEL Nanomachine by Protein Substrates Probed by Paramagnetic Relaxation Enhancement.

Wälti Marielle A MA   Libich David S DS   Clore G Marius GM  

The journal of physical chemistry letters 20180607 12


The chaperonin GroEL is a 800 kDa nanomachine comprising two heptameric rings, each of which encloses a large cavity or folding chamber. The GroEL cycle involves ATP-dependent capping of the cavity by the cochaperone GroES to create a nanocage in which a single protein molecule can fold. We investigate how protein substrates sample the cavity prior to encapsulation by GroES using paramagnetic relaxation enhancement to detect transient, sparsely populated interactions between apo GroEL, paramagne  ...[more]

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