title: Thermodynamics of binding to SH3 domains: the energetic impact of polyproline II (PII) helix formation.
abstract: Although numerous biophysical studies have focused on elucidating the structural and thermodynamic determinants that govern the free energy of binding between various SH3 domains and their putative recognition sequences, a quantitative accounting of the energetics of this interaction has proven enigmatic. Specifically, the binding results in a large and negative change on the standard enthalpy and entropy functions, a result which is inconsistent with the positive values for these quantities that is expected from the hydrophobic nature of the binding pocket. Here, the binding of the C-terminal SH3 domain of Sem-5 to its putative recognition peptide on the Sos (Son of Sevenless) protein is investigated using isothermal titration calorimetry under a variety of temperature and pH conditions. In addition, the energy associated with folding the Sos peptide into the binding competent polyproline II conformation is quantitatively evaluated. These results provide a rationale for the observed discrepancy between the experimental and predicted behavior and indicate that the determinants of binding in this system cannot be ascertained from a static structural representation of the binding process.
authors.affiliation: Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555-1068, USA.
authors.forename: Josephine C
authors.initials: JC
authors.lastname: Ferreon
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hilser
mesh_terms: D000595:Amino Acid Sequence; D019277:Entropy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D020664:Son of Sevenless Proteins / Q000737:chemistry; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D010455:Peptides; D020664:Son of Sevenless Proteins; C011083:polyproline