Thermodynamic Mechanism and Consequences of the Polyproline II (PII) Structural Bias in the Denatured States of Proteins
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- 作者：James B. Hamburger ; Josephine C. Ferreon ; Steven T. Whitten ; and Vincent J. Hilser
- 刊名：Biochemistry
- 出版年：2004
- 出版时间：August 3, 2004
- 年：2004
- 卷：43
- 期：30
- 页码：9790 - 9799
- 全文大小：334K
- 年卷期：v.43,no.30(August 3, 2004)
- ISSN：1520-4995
文摘
A quantitative characterization of the structure and energy of the denatured states of proteinsrepresents 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 (PII)conformation, even when no prolines are present in the sequence. This indicates that the PII conformationis a dominant component of the denatured states of proteins, although a quantitative description of thecomponent enthalpy and entropy functions associated with this conformation (i.e., the thermodynamicmechanism) has thus far proven elusive. An experimental system has been designed that, when analyzedwith high-precision isothermal titration calorimetry, provides direct access to the residue-specificthermodynamics of the PII structure formation in disordered proteins and peptides. Here, it is shown thatthe PII bias is driven by a favorable and significant enthalpy (
chars/Delta.gif" BORDER=0 >h) of -1.7 kcal mol-1 residue-1, whichis partially offset by an unfavorable entropy (Tchars/Delta.gif" BORDER=0 >s) of -0.7 kcal mol-1 residue-1, relative to the ensembleof disordered conformations of the molecule. In addition to impacting dramatically the interpretation ofthermal denaturation experiments, these experimental values form the framework of a quantitative energeticdescription of the denatured states of proteins.
chars/Delta.gif" BORDER=0 >h) of -1.7 kcal mol-1 residue-1, whichis partially offset by an unfavorable entropy (Tchars/Delta.gif" BORDER=0 >s) of -0.7 kcal mol-1 residue-1, relative to the ensembleof disordered conformations of the molecule. In addition to impacting dramatically the interpretation ofthermal denaturation experiments, these experimental values form the framework of a quantitative energeticdescription of the denatured states of proteins.