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A detailed unfolding pathway of a (beta/alpha)8-barrel protein as studied by molecular dynamics simulations.

Authors
  • Akanuma, Satoshi
  • Miyagawa, Hiroh
  • Kitamura, Kunihiro
  • Yamagishi, Akihiko
Type
Published Article
Journal
Proteins Structure Function and Bioinformatics
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 15, 2005
Volume
58
Issue
3
Pages
538–546
Identifiers
PMID: 15614829
Source
Medline
License
Unknown

Abstract

The (beta/alpha)(8)-barrel is the most common protein fold. Similar structural properties for folding intermediates of (beta/alpha)(8)-barrel proteins involved in tryptophan biosynthesis have been reported in a number of experimental studies; these intermediates have the last two beta-strands and three alpha-helices partially unfolded, with other regions of the polypeptide chain native-like in conformation. To investigate the detailed folding/unfolding pathways of these (beta/alpha)(8)-barrel proteins, temperature-induced unfolding simulations of N-(5'-phosphoribosyl)anthranilate isomerase from Escherichia coli were carried out using a special-purpose parallel computer system. Unfolding simulations at five different temperatures showed a sequential unfolding pathway comprised of several events. Early events in unfolding involved disruption of the last two strands and three helices, producing an intermediate ensemble similar to those detected in experimental studies. Then, denaturation of the first two betaalpha units and separation of the sixth strand from the fifth took place independently. The remaining central betaalphabetaalphabeta module persisted the longest during all simulations, suggesting an important role for this module as the incipient folding scaffold. Our simulations also predicted the presence of a nucleation site, onto which several hydrophobic residues condensed forming the foundation for the central betaalphabetaalphabeta module.

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