The PP-fold solution structure of human polypeptide YY and human PYY3-36 as determined by NMR

Biochemistry. 2006 Jul 11;45(27):8350-7. doi: 10.1021/bi060359l.


PYY3-36 is a biopharmaceutical antiobesity agent under development as well as an endogenous satiety hormone, which is generated by dipeptidyl peptidase-IV digestion of polypetide YY (PYY), and in contrast to the parent hormone, PYY is highly selective for the Y2 versus the Y1 receptor. NMR analysis revealed a highly ordered, back-folded structure for human PYY in aqueous solution similar to the classical PP-fold structure of pancreatic polypeptide. The NMR analysis of PYY3-36 also showed a folded structure resembling a PP-fold, which however was characterized by far fewer long distance NOEs than the PP-fold observed in the full-length peptide. This suggests that either a conformational change has occurred in the N-terminal segment of PYY3-36 or that this segments is characterized by larger dynamics. The study supports the notion that the PP-fold is crucial for establishing simultaneous interactions with two subsites in the receptor for binding of, respectively, the N- and C-terminal ends of PYY. The Y2 receptor only requires recognition of the C-terminal segment of the molecule as displayed by the Y2 selective PYY3-36.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments
  • Peptide YY / chemistry*
  • Peptide YY / metabolism
  • Protein Conformation
  • Protein Folding
  • Receptors, Gastrointestinal Hormone / genetics
  • Receptors, Gastrointestinal Hormone / metabolism
  • Solutions / chemistry
  • Transfection


  • Peptide Fragments
  • Receptors, Gastrointestinal Hormone
  • Solutions
  • Peptide YY
  • peptide YY (3-36)

Associated data

  • PDB/2DEZ
  • PDB/2DF0