A 30-residue fragment of the carp granulin-1 protein folds into a stack oftwo beta-hairpins similar to that found in the native protein

Upon air oxidation, a peptide corresponding to the 30-residue N-terminal su bdomain of carp granulin-l spontaneously formed the disulfide pairing obser ved in the native protein. Structural characterization using NMR showed the presence of a defined secondary structure within this peptide. The chemica l shifts for most of the alpha CH protons of the peptide and the protein ar e very similar, and the observed NOE contacts of the peptide strongly resem ble those in the protein. A structure calculation of the peptide using NOE distance constraints indicates that the peptide fragment adopts the same co nformation as formed within the native protein. The 30-residue N-terminal p eptide of carp granulin-l is the first example of an independently folded s tack of two P-hairpins reinforced by two interhairpin disulfide bonds. Two key areas of the structure show a clustering of hydrophobic residues that m ay account for its exceptional conformational stability.