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The effect of the polyproline II (PPII) conformation on the denatured state entropy
Author(s) -
Ferreon Josephine C.,
Hilser Vincent J.
Publication year - 2003
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0237803
Subject(s) - polyproline helix , chemistry , isothermal titration calorimetry , entropy (arrow of time) , conformational entropy , protein folding , crystallography , peptide , stereochemistry , thermodynamics , biochemistry , molecule , physics , organic chemistry
Polyproline II (PPII) is reported to be a dominant conformation in the unfolded state of peptides, even when no prolines are present in the sequence. Here we use isothermal titration calorimetry (ITC) to investigate the PPII bias in the unfolded state by studying the binding of the SH3 domain of SEM‐5 to variants of its putative PPII peptide ligand, Sos. The experimental system is unique in that it provides direct access to the conformational entropy change of the substituted amino acids. Results indicate that the denatured ensemble can be characterized by at least two thermodynamically distinct states, the PPII conformation and an unfolded state conforming to the previously held idea of the denatured state as a random collection of conformations determined largely by hard‐sphere collision. The probability of the PPII conformation in the denatured states for Ala and Gly were found to be significant, ∼30% and ∼10%, respectively, resulting in a dramatic reduction in the conformational entropy of folding.