Thermodynamics of Binding to SH3 Domains: The Energetic Impact of Polyproline II (PII) Helix Formation

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• 作者：Josephine C. Ferreon and Vincent J. Hilser
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：June 22, 2004
• 年：2004
• 卷：43
• 期：24
• 页码：7787 - 7797
• 全文大小：369K
• 年卷期：v.43,no.24(June 22, 2004)
• ISSN：1520-4995

文摘

Although numerous biophysical studies have focused on elucidating the structural andthermodynamic determinants that govern the free energy of binding between various SH3 domains andtheir putative recognition sequences, a quantitative accounting of the energetics of this interaction hasproven enigmatic. Specifically, the binding results in a large and negative change on the standard enthalpyand entropy functions, a result which is inconsistent with the positive values for these quantities that isexpected from the hydrophobic nature of the binding pocket. Here, the binding of the C-terminal SH3domain of Sem-5 to its putative recognition peptide on the Sos (Son of Sevenless) protein is investigatedusing isothermal titration calorimetry under a variety of temperature and pH conditions. In addition, theenergy associated with folding the Sos peptide into the binding competent polyproline II conformation isquantitatively evaluated. These results provide a rationale for the observed discrepancy between theexperimental and predicted behavior and indicate that the determinants of binding in this system cannotbe ascertained from a static structural representation of the binding process.