Unknown

Dataset Information

0

Mapping backbone and side-chain interactions in the transition state of a coupled protein folding and binding reaction.


ABSTRACT: Understanding the mechanism of protein folding requires a detailed knowledge of the structural properties of the barriers separating unfolded from native conformations. The S-peptide from ribonuclease S forms its ?-helical structure only upon binding to the folded S-protein. We characterized the transition state for this binding-induced folding reaction at high resolution by determining the effect of site-specific backbone thioxylation and side-chain modifications on the kinetics and thermodynamics of the reaction, which allows us to monitor formation of backbone hydrogen bonds and side-chain interactions in the transition state. The experiments reveal that ?-helical structure in the S-peptide is absent in the transition state of binding. Recognition between the unfolded S-peptide and the S-protein is mediated by loosely packed hydrophobic side-chain interactions in two well defined regions on the S-peptide. Close packing and helix formation occurs rapidly after binding. Introducing hydrophobic residues at positions outside the recognition region can drastically slow down association.

SUBMITTER: Bachmann A 

PROVIDER: S-EPMC3054012 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mapping backbone and side-chain interactions in the transition state of a coupled protein folding and binding reaction.

Bachmann Annett A   Wildemann Dirk D   Praetorius Florian F   Fischer Gunter G   Kiefhaber Thomas T  

Proceedings of the National Academy of Sciences of the United States of America 20110216 10


Understanding the mechanism of protein folding requires a detailed knowledge of the structural properties of the barriers separating unfolded from native conformations. The S-peptide from ribonuclease S forms its α-helical structure only upon binding to the folded S-protein. We characterized the transition state for this binding-induced folding reaction at high resolution by determining the effect of site-specific backbone thioxylation and side-chain modifications on the kinetics and thermodynam  ...[more]

Similar Datasets

| S-EPMC2754817 | biostudies-literature
| S-EPMC3516198 | biostudies-literature
| S-EPMC2203320 | biostudies-literature
| S-EPMC5909690 | biostudies-literature
| S-EPMC3752112 | biostudies-literature
| S-EPMC2453709 | biostudies-literature
| S-EPMC2271162 | biostudies-literature
| S-EPMC2650303 | biostudies-literature
| S-EPMC2682113 | biostudies-literature
| S-EPMC1479057 | biostudies-literature