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

Peptides and unfolded proteins with the sequence Xaa-Pro-Tyr or Xaa-Pro-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 peptide 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, respectively The two interactions resp ended differently to the denaturants urea and guanidinium chloride; urea had little effect on either, but the second was weakened by guanidinium chloride, whereas the first interaction was strengthened slightly. This explains why such local interactions can be observed in unfolded proteins under strongly denaturing conditions. Interactions such as these are stronger than anticipated in an otherwise disordered peptide; they are probably important for determining the conformational tendencies of unfolded polypeptide chains and may play a role in protein folding. Similar interactions probably occur in protein-ligand interactions.