The folding energy landscape of apoflavodoxin is rugged: Hydrogen exchange reveals nonproductive misfolded intermediates
| Autor: | Carlo P. M. van Mierlo, Monique B. Kamphuis, Yves J. M. Bollen |
|---|---|
| Přispěvatelé: | Structural Biology |
| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Protein Folding spectroscopy topology Protein Conformation Flavodoxin cooperativity pathways Biophysics Biochemie Cooperativity Biochemistry equilibrium Biophysical Phenomena Protein structure Peptide bond Nuclear Magnetic Resonance Biomolecular VLAG Azotobacter vinelandii Multidisciplinary biology Chemistry ensemble Energy landscape dynamics Biological Sciences Deuterium sensitivity Folding (chemistry) Crystallography biology.protein Thermodynamics Protein folding Hydrogen–deuterium exchange Apoproteins azotobacter-vinelandii apoflavodoxin protein Hydrogen |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America 103 (2006) 11 Proceedings of the National Academy of Sciences of the United States of America, 103(11), 4095-4100 Proceedings of the National Academy of Sciences of the United States of America, 103, 4095-4100. National Acad Sciences Bollen, Y J M, Kamphuis, M B & Van Mierlo, C P M 2006, ' The folding energy landscape of apoflavodoxin is rugged: Hydrogen exchange reveals nonproductive misfolded intermediates. ', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, pp. 4095-4100 . https://doi.org/10.1073/pnas.0509133103 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0509133103 |
| Popis: | Many native proteins occasionally form partially unfolded forms (PUFs), which can be detected by hydrogen/deuterium exchange and NMR spectroscopy. Knowledge about these metastable states is required to better understand the onset of folding-related diseases. So far, not much is known about where PUFs reside within the energy landscape for protein folding. Here, four PUFs of the relatively large apoflavodoxin (179 aa) are identified. Remarkably, at least three of them are partially misfolded conformations. The misfolding involves side-chain contacts as well as the protein backbone. The rates at which the PUFs interconvert with native protein have been determined. Comparison of these rates with stopped-flow data positions the PUFs in apoflavodoxin's complex folding energy landscape. PUF1 and PUF2 are unfolding excursions that start from native apoflavodoxin but do not continue to the unfolded state. PUF3 and PUF4 could be similar excursions, but their rates of formation suggest that they are on a dead-end folding route that starts from unfolded apoflavodoxin and does not continue all of the way to native protein. All PUFs detected thus are off the protein's productive folding route. © 2006 by The National Academy of Sciences of the USA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|