One Peptide Reveals the Two Faces of α‑Helix
Unfolding–Folding Dynamics
Version 2 2018-03-30, 18:11
Version 1 2018-03-30, 17:21
Posted on 2018-03-30 - 18:11
The
understanding of fast folding dynamics of single α-helices
comes mostly from studies on rationally designed peptides displaying
sequences with high helical propensity. The folding/unfolding dynamics
and energetics of α-helix conformations in naturally occurring
peptides remains largely unexplored. Here we report the study of a
protein fragment analogue of the C-peptide from bovine pancreatic
ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts
a highly populated helical conformation in aqueous solution. 1H NMR and CD structural studies of RN80 showed that α-helix
formation displays a pH-dependent bell-shaped curve, with a maximum
near pH 5, and a large decrease in helical content in alkaline pH.
The main forces stabilizing this short α-helix were identified
as a salt bridge formed between Glu-2 and Arg-10 and the cation−π
interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2
or protonation of His-12 are essential for the RN80 α-helix
stability. In the present study, RN80 folding and unfolding were triggered
by laser-induced pH jumps and detected by time-resolved photoacoustic
calorimetry (PAC). The photoacid proton release, amino acid residue
protonation, and unfolding/folding events occur at different time
scales and were clearly distinguished using time-resolved PAC. The
partial unfolding of the RN80 α-helix, due to protonation of
Glu-2 and consequent breaking of the stabilizing salt bridge between
Glu-2 and Arg-10, is characterized by a concentration-independent
volume expansion in the sub-microsecond time range (0.8 mL mol–1, 369 ns). This small volume expansion reports the
cost of peptide backbone rehydration upon disruption of a solvent-exposed
salt bridge, as well as backbone intrinsic expansion. On the other
hand, RN80 α-helix folding triggered by His-12 protonation and
subsequent formation of a cation−π interaction leads
to a microsecond volume contraction (−6.0 mL mol–1, ∼1.7 μs). The essential role of two discrete side
chain interactions, a salt bridge, and in particular a single cation−π
interaction in the folding dynamics of a naturally occurring α-helix
peptide is uniquely revealed by these data.
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Jesus, Catarina
S. H.; Cruz, Pedro F.; Arnaut, Luis G.; M. M. Brito, Rui; Serpa, Carlos (2018). One Peptide Reveals the Two Faces of α‑Helix
Unfolding–Folding Dynamics. ACS Publications. Collection. https://doi.org/10.1021/acs.jpcb.8b00229
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AUTHORS (5)
CJ
Catarina
S. H. Jesus
PC
Pedro F. Cruz
LA
Luis G. Arnaut
RM
Rui M. M. Brito
CS
Carlos Serpa
KEYWORDS
acid residue protonationdynamicPACpH-dependent bell-shaped curveα- helix formation displaysvolume expansion reportsRN 80 α- helix stabilitytime-resolved photoacoustic calorimetry1 H NMRacid residue peptideRN 80α- helix peptideGlu -2helicalpeptide backbone rehydrationprotein fragment analogueside chain interactionslaser-induced pH jumpsphotoacid proton releaseα- helix conformationscationconcentration-independent volume expansionRN 80 α- helixsalt bridgesolvent-exposed salt bridge