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α-Helix folding in the presence of structural constraints.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 7/15/2008, Vol. 105 Issue 28, p9588-9593, 6p, 1 Diagram, 3 Graphs
- Publication Year :
- 2008
-
Abstract
- We have investigated the site-specific folding kinetics of a photo-switchable cross-linked α-helical peptide by using single <superscript>13</superscript>C = <superscript>18</superscript>O isotope labeling together with time-resolved IR spectroscopy. We observe that the folding times differ from site to site by a factor of eight at low temperatures (6°C), whereas at high temperatures (45°C), the spread is considerably smaller. The trivial sum of the site signals coincides with the overall folding signal of the unlabeled peptide. and different sites fold in a noncooperative manner. Moreover, one of the sites exhibits a decrease of hydrogen bonding upon folding, implying that the unfolded state at low temperature is not unstructured. Molecular dynamics simulations at low temperature reveal a, stretched-exponential behavior which originates from parallel folding routes that start from a kinetically partitioned unfolded ensemble. Different metastable structures (i.e., traps) in the unfolded ensemble have a different ratio of loop and helical content. Control simulations of the peptide at high temperature, as well as without the cross-linker at low temperature, show faster and simpler (i.e., single-exponential) folding kinetics. The experimental and simulation results together provide strong evidence that the rate-limiting step in formation of a structurally constrained α-helix is the escape from heterogeneous traps rather than the nucleation rate. This conclusion has important implications for an α-helical segment within a protein, rather than an isolated α-helix, because the cross-linker is a structural constraint similar to those present during the folding of a globular protein. [ABSTRACT FROM AUTHOR]
- Subjects :
- INFRARED spectroscopy
PEPTIDES
NUCLEATION
HYDROGEN
TEMPERATURE
GLOBULAR proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 105
- Issue :
- 28
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 33399763
- Full Text :
- https://doi.org/10.1073/pnas.0712099105