One of the necessary conditions for a protein to be foldable is the presence of a complete set of "folding elements" (FEs) that are short, contiguous peptide segments distributed over an @entity535 sequence. The FE-assembly model of protein folding has been proposed, in which the FEs play a role in guiding structure formation through FE-FE interactions early in folding. However, two major issues remain to be clarified regarding the roles of the FEs in determining protein foldability. Are the FEs AFUs that can form nativelike structures in isolation? Is the presence of only the FEs without mutual connections a sufficient condition for a protein to be foldable? Here, we address these questions using peptide fragments corresponding to the FEs of @entity39297 from @entity526 . We show by CD measurement that the FE peptides are unfolded under the native conditions, and some of them have the propensities toward non-native helices. @entity601 simulations also show the non-native helical propensities of the peptides, and the helix contents estimated from the simulations are well correlated with those estimated from the CD in TFE. Thus, the FEs of @entity39297 are not AFUs, suggesting the importance of the FEs in nonlocal interactions. We also show that equimolar mixtures of the FE peptides do not induce any structural formation. Therefore, mutual connections between the FEs, which should strengthen the nonlocal FE-FE interactions, are also one of the necessary conditions for a protein to be foldable.

Peptide fragment studies on the folding elements of dihydrofolate reductase from XXXX .

@entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity39297 :: ('13906554', 'Gene') :: ['DHFR'] @entity526 :: ('562', 'Species') :: ['Escherichia coli'] @entity601 :: ('MESH:D009436', 'Disease') :: ['MD']
@entity526 :: (562,Species) :: ['Escherichia coli']
