The C-terminal region of Opisthorchis viverrini granulin-1 promotes cell proliferation in the absence of regular secondary structure

Topical application of granulin-derived peptides has the potential to alleviate the burden of chronic wounds. Granulins are a family of growth factor proteins that generally contain six disulfide bonds and are found in most organisms. They have diverse sequences and complex structure–function relationships. Select examples are potent wound healing agents, making it important to improve our understanding of how granulins fold and the structural features critical for bioactivity. We have previously shown that fragments corresponding to the N-terminal region of the parasite granulin, Ov-GRN-1, can fold autonomously even with a non-native disulfide bond and still have well-defined structures. Here, we show that this phenomenon appears unique to the N-terminal region, as a peptide corresponding to the C-terminal fragment of Ov-GRN-1 does not fold independently in an analogous manner to the N-terminal region. Despite a lack of structure in the C-terminal granulin fragment, this peptide promotes cell proliferation, indicating that the sequence might be more important than the three-dimensional structure for Ov-GRN-1 wound-healing bioactivity.