THE PHYSICAL-PROPERTIES OF LOCAL INTERACTIONS OF TYROSINE RESIDUES INPEPTIDES AND UNFOLDED PROTEINS

Peptides and unfolded proteins with the sequence Xaa-Pro-Tyr or Xaa-Pr o-Phe have a relatively strong local interaction, present about 64% of the time at 10 degrees C, of the aromatic ring with the side-chain of Pro and the (CH)-H-alpha of residue Xaa, but only when the Xaa-Pro pe ptide bond is cis. With the sequence Tyr-Yaa-Gly (Yaa not equal Pro), there is a somewhat weaker interaction, present about 26% of the time, of the aromatic ring with the Gly residue. When present together, in the sequence Xaa-Pro-Tyr-Yaa-Gly, the two interactions of the Tyr side -chain compete and have the expected strengths. Both interactions have an enthalpic basis, with enthalpies of about -3 and -2.8 kcal/mol, re spectively The two interactions resp ended differently to the denatura nts urea and guanidinium chloride; urea had little effect on either, b ut the second was weakened by guanidinium chloride, whereas the first interaction was strengthened slightly. This explains why such local in teractions can be observed in unfolded proteins under strongly denatur ing conditions. Interactions such as these are stronger than anticipat ed in an otherwise disordered peptide; they are probably important for determining the conformational tendencies of unfolded polypeptide cha ins and may play a role in protein folding. Similar interactions proba bly occur in protein-ligand interactions.