Thermodynamic mechanism and consequences of the polyproline II (PII) structural bias in the denatured states of proteins.
A quantitative characterization of the structure and energy of the denatured states of proteins represents the cornerstone to a molecular-level understanding of both protein stability and fold specificity. Recent studies have revealed a significant bias in unstructured peptides toward the polyproline II (P(II)) conformation, even when no prolines are present in the sequence. This indicates that the P(II) conformation is a dominant component of the denatured states of proteins, although a quantitative description of the component enthalpy and entropy functions associated with this conformation (i.e., the thermodynamic mechanism) has thus far proven elusive. An experimental system has been designed that, when analyzed with high-precision isothermal titration calorimetry, provides direct access to the residue-specific thermodynamics of the P(II) structure formation in disordered proteins and peptides. Here, it is shown that the P(II) bias is driven by a favorable and significant enthalpy (Deltah) of -1.7 kcal mol(-1) residue(-1), which is partially offset by an unfavorable entropy (TDeltas) of -0.7 kcal mol(-1) residue(-1), relative to the ensemble of disordered conformations of the molecule. In addition to impacting dramatically the interpretation of thermal denaturation experiments, these experimental values form the framework of a quantitative energetic description of the denatured states of proteins.
Department of Human Biological Chemistry and Genetics, and Sealy Center for Structural Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
James B
JB
Hamburger
Josephine C
JC
Ferreon
Steven T
ST
Whitten
Vincent J
VJ
Hilser
D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry; D002151:Calorimetry / Q000379:methods / Q000706:statistics & numerical data; D019277:Entropy; D008956:Models, Chemical; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011336:Probability; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D020664:Son of Sevenless Proteins / Q000737:chemistry; D013816:Thermodynamics
D029742:Caenorhabditis elegans Proteins; D009842:Oligopeptides; D010455:Peptides; C085751:Sem-5 protein, C elegans; D020664:Son of Sevenless Proteins; C011083:polyproline