A peptide derived from the C‐terminal part of a plant cysteine protease folds into a stack of two β‐hairpins,a scaffold present in the emerging family of granulin‐like growth factors

Abstract: A 35 amino acid residue peptide corresponding to the N‐terminal subdomain of the granulin‐like repeat from rice oryzain β was synthesized and regioselectively oxidized to produce a species with a [1–3, 2–4] disulfide‐pairing pattern. The resulting peptide was studied in solution using NMR and was shown to adopt the tertiary topology of a stack of two β‐hairpins found in the emerging family of granulin‐like growth factors. Because of the longer second β‐hairpin, the overall conformation of the peptide is somewhat more flexible than that of its well‐structured carp granulin‐1 analog. Except for the cysteine alignment, there is very little sequence homology between granulin‐like growth factors from the animal kingdom and the granulin‐like repeats at the C‐termini of plant cysteine proteases. Therefore, the stack of two β‐hairpins may be a conserved three‐dimensional organization of the granulin‐like repeats from evolutionary distant sources with a significant role in specific protein–protein interactions.