ArticleProceedings of the National Academy of Sciences of the United States of America2008
Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Allosteric and energetic remodeling of a PDZ domain by protein domain extensions.Nature communications · 2026Article
- Topological determinants in protein folding dynamics: a comparative analysis of metamorphic proteins.Biology direct · 2025Article
- MoCHI: neural networks to fit interpretable models and quantify energies, energetic couplings, epistasis, and allostery from deep mutational scanning data.Genome biology · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Characterization of early and late transition states of the folding pathway of a SH2 domain.Protein science : a publication of the Protein Society · 2022Article
- Article
- A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands.Biomolecules · 2021Article
- Fuzziness and Frustration in the Energy Landscape of Protein Folding, Function, and Assembly.Accounts of chemical research · 2021Review
- Hidden kinetic traps in multidomain folding highlight the presence of a misfolded but functionally competent intermediate.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Conformational Plasticity Vista of PDZ Domains.Life (Basel, Switzerland) · 2020Review
- Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls.International journal of molecular sciences · 2020Review
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Denaturants Alter the Flux through Multiple Pathways in the Folding of PDZ Domain.The journal of physical chemistry. B · 2018Article
- Addressing the role of the α-helical extension in the folding of the third PDZ domain from PSD-95.Scientific reports · 2017Article
- Evolution of a protein folding nucleus.Protein science : a publication of the Protein Society · 2016Article
- Common features in the unfolding and misfolding of PDZ domains and beyond: the modulatory effect of domain swapping and extra-elements.Scientific reports · 2016Article
- Understanding the frustration arising from the competition between function, misfolding, and aggregation in a globular protein.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Sequence analysis on the information of folding initiation segments in ferredoxin-like fold proteins.BMC structural biology · 2014Article
- The folding of a family of three-helix bundle proteins: spectrin R15 has a robust folding nucleus, unlike its homologous neighbours.Journal of molecular biology · 2014Article
- The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.PloS one · 2014Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The energy landscape theory provides a general framework for describing protein folding reactions. Because a large number of studies, however, have focused on two-state proteins with single well-defined folding pathways and without detectable intermediates, the extent to which free energy landscapes are shaped up by the native topology at the early stages of the folding process has not been fully characterized experimentally. To this end, we have investigated the folding mechanisms of two homologous three-state proteins, PTP-BL PDZ2 and PSD-95 PDZ3, and compared the early and late transition states on their folding pathways. Through a combination of Phi value analysis and molecular dynamics simulations we obtained atomic-level structures of the transition states of these homologous three-state proteins and found that the late transition states are much more structurally similar than the early ones. Our findings thus reveal that, while the native state topology defines essentially in a unique way the late stages of folding, it leaves significant freedom to the early events, a result that reflects the funneling of the free energy landscape toward the native state.
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