HD-exchange motions of ribosomal protein S6 are insensitive to reversal of the protein-folding pathway

An increasing number of protein structures are found to encompass multiple folding nuclei, allowing their structures to be formed by several competing pathways. A typical example is the ribosomal protein S6, which comprises two folding nuclei (σ1 and σ2) defining two competing pathways in the foldin...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-12, Vol.106 (51), p.21619-21624
Main Authors: Haglund, Ellinor, Lind, Jesper, Öman, Tommy, Öhman, Anders, Mäler, Lena, Oliveberg, Mikael
Format: Article
Language:English
Subjects:
Amides
Biochemistry
Biokemi
Biological Sciences
Chemistry
circular permutation
energy landscape
Exchange rates
Hydrogen
Ion exchange
Kemi
Models, Molecular
Molecular structure
Molecules
NATURAL SCIENCES
NATURVETENSKAP
protein dynamics
Protein Folding
Proteins
Protons
Ribosomal Protein S6 - chemistry
Ribosomal proteins
Solvents
Topology
transition state
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Summary:An increasing number of protein structures are found to encompass multiple folding nuclei, allowing their structures to be formed by several competing pathways. A typical example is the ribosomal protein S6, which comprises two folding nuclei (σ1 and σ2) defining two competing pathways in the folding energy landscape: σ1 → σ2 and σ2 → σ1. The balance between the two pathways, and thus the order of folding events, is easily controlled by circular permutation. In this study, we make use of this ability to manipulate the folding pathway to demonstrate that the dynamic motions of the S6 structure are independent of how the protein folds. The HD-exchange protection factors remain the same upon complete reversal of the folding order. The phenomenon arises because the HD-exchange motions and the high-energy excitations controlling the folding pathway occur at separated free-energy levels: the Boltzmann distribution of unproductive unfolding attempts samples all unfolding channels in parallel, even those that end up in excessively high barriers. Accordingly, the findings provide a simple rationale for how to interpret native-state dynamics without the need to invoke fluctuations off the normal unfolding reaction coordinate.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.0907665106