The unprocessed pro-form of the NGF (nerve growth factor), proNGF (NGF precursor, without signal peptide), has been suggested to have additional functions distinct from its role as a promoter of protein folding, i.e. apoptosis and/or neurotrophic activity. Aiming to gain insights into the specific molecular interactions that mediate proNGF biological activity and into the structural determinants stabilizing its pro-region, rm-proNGF (recombinant mouse proNGF) was expressed in Escherichia coli, refolded in vitro and characterized by physicochemical methods. X-ray solution scattering measurements (small angle X-ray scattering) revealed that rm-proNGF is dimeric in solution and appears to be anisometric when compared with the compact structure of the NGF dimer. Two structural models, a globular crab-like shape and an elongated rod-like shape, equally fit to the experimental results, pointing to an intrinsically structural disordered pro-region of NGF. The models obtained allowed the interpretation of TrkA (tropomyosin receptor kinase A) binding and activation assays in cell cultures, shedding new light on the key role of proNGF in neuronal survival and neurodegeneration.
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August 2006
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Conference Article|
July 21 2006
Structural and functional properties of mouse proNGF
F. Paoletti;
F. Paoletti
1
*SISSA/ISAS (Scuola Internazionale Superiore di Studi Avanzati/International School of Advanced Studies), Trieste, Italy
1To whom correspondence should be addressed (email paoletti@sissa.it).
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P.V. Konarev;
P.V. Konarev
†EMBL (European Molecular Biology Laboratory), Hamburg Outstation, Hamburg, Germany
‡Institute of Crystallography, Russian Academy of Sciences, Moscow, Russia
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S. Covaceuszach;
S. Covaceuszach
§LayLine Genomics, Rome, Italy
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E. Schwarz;
E. Schwarz
∥Institut für Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany
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A. Cattaneo;
A. Cattaneo
*SISSA/ISAS (Scuola Internazionale Superiore di Studi Avanzati/International School of Advanced Studies), Trieste, Italy
¶European Brain Research Institute, Rome, Italy
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D. Lamba;
D. Lamba
**Istituto di Cristallografia – CNR (Consiglio Nazionale delle Ricerche), Area Science Park, Trieste, Italy
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D.I. Svergun
D.I. Svergun
†EMBL (European Molecular Biology Laboratory), Hamburg Outstation, Hamburg, Germany
‡Institute of Crystallography, Russian Academy of Sciences, Moscow, Russia
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Publisher: Portland Press Ltd
Received:
April 07 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (4): 605–606.
Article history
Received:
April 07 2006
Citation
F. Paoletti, P.V. Konarev, S. Covaceuszach, E. Schwarz, A. Cattaneo, D. Lamba, D.I. Svergun; Structural and functional properties of mouse proNGF. Biochem Soc Trans 1 August 2006; 34 (4): 605–606. doi: https://doi.org/10.1042/BST0340605
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