Native-like structure of a protein-folding intermediate bound to the chaperonin GroEL
AUTOR(ES)
Goldberg, Matthew S.
FONTE
The National Academy of Sciences of the USA
RESUMO
The chaperonin GroEL binds nonnative proteins in its central channel through hydrophobic interactions and initiates productive folding in this space underneath bound cochaperone, GroES, in the presence of ATP. The questions of where along the folding pathway a protein is recognized by GroEL, and how much structure is present in a bound substrate have remained subjects of discussion, with some experiments suggesting that bound forms are fully unfolded and others suggesting that bound species are partially structured. Here we have studied a substrate protein, human dihydrofolate reductase (DHFR), observing in stopped-flow fluorescence experiments that it can rapidly bind to GroEL at various stages of folding. We have also analyzed the structure of the GroEL-bound protein using hydrogen–deuterium exchange and NMR spectroscopy. The pattern and magnitude of amide proton protection indicate that the central parallel β-sheet found in native DHFR is present in a moderately stable state in GroEL-bound DHFR. Considering that the β-strands are derived from distant parts of the primary structure, this suggests that a native-like global topology is also present. We conclude that significant native-like structure is present in protein-folding intermediates bound to GroEL.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19747Documentos Relacionados
- The protein-folding activity of chaperonins correlates with the symmetric GroEL14(GroES7)2 heterooligomer.
- Phylogeny of protein-folding trajectories reveals a unique pathway to native structure
- Native-like in vivo folding of a circularly permuted jellyroll protein shown by crystal structure analysis.
- Specificity of native-like interhelical hydrophobic contacts in the apomyoglobin intermediate
- GroEL binds a late folding intermediate of phage P22 coat protein