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

http://www.ncbi.nlm.nih.gov/pubmed/20515035

dc.identifier.eissn

1520-4995

dc.identifier.uri

https://hdl.handle.net/10161/4008

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

http://www.ncbi.nlm.nih.gov/pubmed/20515035

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
279197300023.pdf
Size:
2.2 MB
Format:
Adobe Portable Document Format