title: Conformational plasticity of proNGF.
abstract: Nerve Growth Factor is an essential protein that supports neuronal survival during development and influences neuronal function throughout adulthood, both in the central and peripheral nervous system. The unprocessed precursor of NGF, proNGF, seems to be endowed with biological functions distinct from those of the mature protein, such as chaperone-like activities and apoptotic and/or neurotrophic properties. We have previously suggested, based on Small Angle X-ray Scattering data, that recombinant murine proNGF has features typical of an intrinsically unfolded protein. Using complementary biophysical techniques, we show here new evidence that clarifies and widens this hypothesis through a detailed comparison of the structural properties of NGF and proNGF. Our data provide direct information about the dynamic properties of the pro-peptide and indicate that proNGF assumes in solution a compact globular conformation. The N-terminal pro-peptide extension influences the chemical environment of the mature protein and protects the protein from proteolytic digestion. Accordingly, we observe that unfolding of proNGF involves a two-steps mechanism. The distinct structural properties of proNGF as compared to NGF agree with and rationalise a different functional role of the precursor.
authors.affiliation: European Brain Research Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoletti
authors.forename: Francesca
authors.initials: F
authors.lastname: Malerba
authors.forename: Geoff
authors.initials: G
authors.lastname: Kelly
authors.forename: Sylvie
authors.initials: S
authors.lastname: Noinville
authors.forename: Doriano
authors.initials: D
authors.lastname: Lamba
authors.forename: Antonino
authors.initials: A
authors.lastname: Cattaneo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003470:Culture Media; D004058:Diffusion; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008970:Molecular Weight; D020932:Nerve Growth Factor / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011498:Protein Precursors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D058849:Protein Refolding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D059748:Proteolysis; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D014357:Trypsin / Q000378:metabolism
chemical_list: D003470:Culture Media; D010455:Peptides; D011498:Protein Precursors; D012996:Solutions; C489226:pro-nerve growth factor, mouse; D020932:Nerve Growth Factor; D014357:Trypsin