Cross-Validation of the Structure of a Transiently Formed and Low Populated FF Domain Folding Intermediate Determined by Relaxation Dispersion NMR and CS-Rosetta
| Autor: | Lewis E. Kay, Julia Barette, Algirdas Velyvis, Tomasz L. Religa, Dmitry M. Korzhnev |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation Chemistry Relaxation (NMR) Nuclear magnetic resonance spectroscopy of nucleic acids Surfaces Coatings and Films Folding (chemistry) Crystallography Protein structure Materials Chemistry Native state Humans Intermediate state Protein folding Transverse relaxation-optimized spectroscopy Physical and Theoretical Chemistry Carrier Proteins Databases Protein Nuclear Magnetic Resonance Biomolecular |
| Zdroj: | The Journal of Physical Chemistry B. 116:6637-6644 |
| ISSN: | 1520-5207 1520-6106 1312-1316 |
| DOI: | 10.1021/jp209974f |
| Popis: | We have recently reported the atomic resolution structure of a low populated and transiently formed on-pathway folding intermediate of the FF domain from human HYPA/FBP11 [Korzhnev, D. M.; Religa, T. L.; Banachewicz, W.; Fersht, A. R.; Kay, L.E. Science 2011, 329, 1312-1316]. The structure was determined on the basis of backbone chemical shift and bond vector orientation restraints of the invisible intermediate state measured using relaxation dispersion nuclear magnetic resonance (NMR) spectroscopy that were subsequently input into the database structure determination program, CS-Rosetta. As a cross-validation of the structure so produced, we present here the solution structure of a mimic of the folding intermediate that is highly populated in solution, obtained from the wild-type domain by mutagenesis that destabilizes the native state. The relaxation dispersion/CS-Rosetta structures of the intermediate are within 2 Å of those of the mimic, with the nonnative interactions in the intermediate also observed in the mimic. This strongly confirms the structure of the FF domain folding intermediate, in particular, and validates the use of relaxation dispersion derived restraints in structural studies of invisible excited states, in general. |
| Databáze: | OpenAIRE |
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