Differences in the folding transition state of ubiquitin indicated by φ and ψ analyses
- 2 December 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (50) , 17377-17382
- https://doi.org/10.1073/pnas.0407683101
Abstract
We compare the folding transition state (TS) of ubiquitin previously identified by using psi analysis to that determined by using analysis. Both methods attempt to identify interactions and their relative populations at the rate-limiting step for folding. The TS ensemble derived from psi analysis has an extensive native-like chain topology, with a four-stranded beta-sheet network and a portion of the major helix. According to analysis, however, the TS is much smaller and more polarized, with only a local helix/hairpin motif. We find that structured regions can have values far from unity, the canonical value for such sites, because of structural relaxation of the TS. Consequently, these sites may be incorrectly interpreted as contributing little to the structure of the TS. These results stress the need for caution when interpreting and drawing conclusions from analysis alone and highlight the need for more specific tools for examining the structure and energetics of the TS ensemble.Keywords
This publication has 34 references indexed in Scilit:
- The folding of an enzyme: I. Theory of protein engineering analysis of stability and pathway of protein foldingPublished by Elsevier ,2004
- Is an intermediate state populated on the folding pathway of ubiquitin?FEBS Letters, 2004
- Discerning the Structure and Energy of Multiple Transition States in Protein Folding using ψ-AnalysisJournal of Molecular Biology, 2004
- Early Collapse is not an Obligate Step in Protein FoldingJournal of Molecular Biology, 2004
- Origin of Unusual φ-values in Protein Folding: Evidence Against Specific Nucleation SitesJournal of Molecular Biology, 2003
- Specific Non-Native Hydrophobic Interactions in a Hidden Folding Intermediate: Implications for Protein FoldingBiochemistry, 2003
- Fast and Slow Intermediate Accumulation and the Initial Barrier Mechanism in Protein FoldingJournal of Molecular Biology, 2002
- Protein Folding Kinetics Beyond the Φ Value: Using Multiple Amino Acid Substitutions to Investigate the Structure of the SH3 Domain Folding Transition StateJournal of Molecular Biology, 2002
- The single helix in protein L is largely disrupted at the rate-limiting step in foldingJournal of Molecular Biology, 1998
- Contact order, transition state placement and the refolding rates of single domain proteins 1 1Edited by P. E. WrightJournal of Molecular Biology, 1998