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

• 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
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0907665106

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.