The mature part of proNGF induces the structure of its pro-peptide

• Published in: FEBS letters Vol. 566; no. 1; pp. 207 - 212
• Main Authors: Kliemannel, Marco, Rattenholl, Anke, Golbik, Ralph, Balbach, Jochen, Lilie, Hauke, Rudolph, Rainer, Schwarz, Elisabeth
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 21.05.2004
• Subjects: Circular Dichroism; Cross-Linking Reagents - chemistry; Cystine knot proteins; Dimerization; Disulfides - chemistry; Escherichia coli - metabolism; Guanidine - chemistry; Humans; Models, Molecular; Nerve Growth Factors - chemistry; Nerve Growth Factors - genetics; NGF; Nuclear Magnetic Resonance, Biomolecular; Oxidative folding; Pro-peptide stimulated folding; Protein Denaturation; Protein Precursors - chemistry; Protein Precursors - genetics; Protein Renaturation; Protein Structure, Secondary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Spectrometry, Fluorescence; Pro-peptide stimulated folding; Cystine knot proteins; NGF; Oxidative folding
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.04.034

Human nerve growth factor (NGF) belongs to the structural family of cystine knot proteins, characterized by a disulfide pattern in which one disulfide bond threads through a ring formed by a pair of two other disulfides connecting two adjacent β-strands. Oxidative folding of NGF revealed that the pro-peptide of NGF stimulates in vitro structure formation. In order to learn more about this folding assisting protein fragment, a biophysical analysis of the pro-peptide structure has been performed. While proNGF is a non-covalent homodimer, the isolated pro-peptide is monomeric. No tertiary contacts stabilize the pro-peptide in its isolated form. In contrast, the pro-peptide appears to be structured when bound to the mature part. The results presented here demonstrate that the mature part stabilizes the structure in the pro-peptide region. This is the first report that provides a biophysical analysis of a pro-peptide of the cystine knot protein family.