Dynamics of Unfolded Polypeptide Chains as Model for the Earliest Steps in Protein Folding

The rate of formation of intramolecular interactions in unfolded proteins determines how fast conformational space can be explored during folding. Characterization of the dynamics of unfolded proteins is therefore essential for the understanding of the earliest steps in protein folding. We used trip...

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Bibliographic Details
Published in:Journal of molecular biology 2003-09, Vol.332 (1), p.265-274
Main Authors: Krieger, Florian, Fierz, Beat, Bieri, Oliver, Drewello, Mario, Kiefhaber, Thomas
Format: Article
Language:English
Subjects:
Amino Acid Sequence
chain dynamics
Energy Transfer
Glycine - chemistry
intrachain diffusion
Molecular Structure
Peptides - chemistry
Protein Conformation
Protein Folding
triplet–triplet transfer
unfolded proteins
Water - chemistry
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Summary:The rate of formation of intramolecular interactions in unfolded proteins determines how fast conformational space can be explored during folding. Characterization of the dynamics of unfolded proteins is therefore essential for the understanding of the earliest steps in protein folding. We used triplet–triplet energy transfer to measure formation of intrachain contacts in different unfolded polypeptide chains. The time constants (1/ k) for contact formation over short distances are almost independent of chain length, with a maximum value of about 5 ns for flexible glycine-rich chains and of 12 ns for stiffer chains. The rates of contact formation over longer distances decrease with increasing chain length, indicating different rate-limiting steps for motions over short and long chain segments. The effect of the amino acid sequence on local chain dynamics was probed by using a series of host-guest peptides. Formation of local contacts is only sixfold slower around the stiffest amino acid (proline) compared to the most flexible amino acid (glycine). Good solvents for polypeptide chains like EtOH, GdmCl and urea were found to slow intrachain diffusion and to decrease chain stiffness. These data allow us to determine the time constants for formation of the earliest intrachain contacts during protein folding.
ISSN:0022-2836
1089-8638
DOI:10.1016/S0022-2836(03)00892-1