Short-lived alpha-helical intermediates in the folding of beta-sheet proteins.
| dc.contributor.author | Chen, E | |
| dc.contributor.author | Everett, ML | |
| dc.contributor.author | Holzknecht, ZE | |
| dc.contributor.author | Holzknecht, RA | |
| dc.contributor.author | Lin, SS | |
| dc.contributor.author | Bowles, DE | |
| dc.contributor.author | Parker, W | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2011-06-21T17:22:09Z | |
| dc.date.issued | 2010-07-06 | |
| dc.description.abstract | Several lines of evidence point strongly toward the importance of highly alpha-helical intermediates in the folding of all globular proteins, regardless of their native structure. However, experimental refolding studies demonstrate no observable alpha-helical intermediate during refolding of some beta-sheet proteins and have dampened enthusiasm for this model of protein folding. In this study, beta-sheet proteins were hypothesized to have potential to form amphiphilic helices at a period of <3.6 residues/turn that matches or exceeds the potential at 3.6 residues/turn. Hypothetically, such potential is the basis for an effective and unidirectional mechanism by which highly alpha-helical intermediates might be rapidly disassembled during folding and potentially accounts for the difficulty in detecting highly alpha-helical intermediates during the folding of some proteins. The presence of this potential was confirmed, indicating that a model entailing ubiquitous formation of alpha-helical intermediates during the folding of globular proteins predicts previously unrecognized features of primary structure. Further, the folding of fatty acid binding protein, a predominantly beta-sheet protein that exhibits no apparent highly alpha-helical intermediate during folding, was dramatically accelerated by 2,2,2-trifluoroethanol, a solvent that stabilizes alpha-helical structure. This observation suggests that formation of an alpha-helix can be a rate-limiting step during folding of a predominantly beta-sheet protein and further supports the role of highly alpha-helical intermediates in the folding of all globular proteins. | |
| dc.description.version | Version of Record | |
| dc.identifier | ||
| dc.identifier.eissn | 1520-4995 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.language.iso | en_US | |
| dc.publisher | American Chemical Society (ACS) | |
| dc.relation.ispartof | Biochemistry | |
| dc.relation.isversionof | 10.1021/bi100288q | |
| dc.relation.journal | Biochemistry | |
| dc.subject | Fatty Acid-Binding Proteins | |
| dc.subject | Kinetics | |
| dc.subject | Models, Molecular | |
| dc.subject | Protein Folding | |
| dc.subject | Protein Structure, Secondary | |
| dc.subject | Solvents | |
| dc.title | Short-lived alpha-helical intermediates in the folding of beta-sheet proteins. | |
| dc.title.alternative | ||
| dc.type | Journal article | |
| duke.contributor.orcid | Bowles, DE|0000-0002-2781-1300 | |
| duke.contributor.orcid | Parker, W|0000-0003-3644-9152 | |
| duke.date.pubdate | 2010-7-6 | |
| duke.description.issue | 26 | |
| duke.description.volume | 49 | |
| pubs.author-url | ||
| pubs.begin-page | 5609 | |
| pubs.end-page | 5619 | |
| pubs.issue | 26 | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Immunology | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Surgery | |
| pubs.organisational-group | Surgery, Cardiovascular and Thoracic Surgery | |
| pubs.organisational-group | Surgery, Surgical Sciences | |
| pubs.publication-status | Published | |
| pubs.volume | 49 |