1 research outputs found
Nascent Hairpins in Proteins: Identifying Turn Loci and Quantitating Turn Contributions to Hairpin Stability
Many
factors influence the stability of hairpins that could appear
as foldons in partially folded states of proteins; of these, the propensity
of certain amino acid sequences to favor conformations that serve
to align potential β-strands for antiparallel association is
likely the dominant feature. Quantitating turn propensities is viewed
as the first step in developing an algorithm for locating nascent
hairpins in protein sequences. Such nascent hairpins can serve to
accelerate protein folding or, if they represent structural elements
that differ from the final folded state, as kinetic traps. We have
measured these “turn propensities” for the two most
common turn types using a series of model peptide hairpins with four-
and six-residue loops connecting the associated β-strands. Loops
of four to six residues with specific turn sequences containing only
natural l-amino acids and glycine can provide as much as
15 kJ/mol of hairpin stabilization versus loops lacking the defined
turn loci. Single-site mutations within some of the optimal connecting
loops can have ΔΔ<i>G</i> effects as large as
9–10 kJ/mol on hairpin stability. In contrast to the near universal
II′/I′ turns of model hairpins, a number of hairpin-supporting
XZZG sequence β-turns with α<sub>R</sub> and/or γ<sub>R</sub> configurations at the ZZ unit were found. A series of turn
replacements (four-residue β-turns replaced by sequences that
favor five- and six-residue reversing loops) using identical strands
in our model systems have confirmed that several sequences have intrinsic
turn propensities that could favor β-strand association in a
non-native strand register and thus serve as kinetic traps. These
studies also indicate that aryl residues immediately flanking a turn
sequence can alter relative turn propensities by as much as 9–11
kJ/mol and will need to be a part of any nascent hairpin recognition
algorithm