Proteomics

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Effects of ATP binding on the conformational flexibility of proNGF

ABSTRACT: Nerve growth factor (NGF) is involved in the maintenance and growth of specific neuronal populations whereas its precursor, proNGF, shows opposite properties, like being involved in apoptosis. NGF/proNGF imbalance is linked to neurodegeneration. Here, we show that ATP binds to proNGF inducing an overall proNGF shape change, throughout a local conformational rearrangement of the flexible pro-peptide domain. This suggests a functional role for ATP in the modulation of proNGF/NGF physiological homeostasis.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Antonio Calabrese  

LAB HEAD: Antonio Calabrese

PROVIDER: PXD035625 | Pride | 2023-11-16

REPOSITORIES: Pride

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Action DRS
NGF.DnX Other
fbsaca_220127_hdx1_01.raw.zip Raw
fbsaca_220127_hdx1_03.raw.zip Raw
fbsaca_220127_hdx1_05.raw.zip Raw
fbsaca_220127_hdx1_07.raw.zip Raw
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Publications

Distinct conformational changes occur within the intrinsically unstructured pro-domain of pro-Nerve Growth Factor in the presence of ATP and Mg<sup>2</sup>.

Paoletti Francesca F   Covaceuszach Sonia S   Cassetta Alberto A   Calabrese Antonio N AN   Novak Urban U   Konarev Petr P   Grdadolnik Jože J   Lamba Doriano D   Golič Grdadolnik Simona S  

Protein science : a publication of the Protein Society 20230201 2

Nerve growth factor (NGF), the prototypical neurotrophic factor, is involved in the maintenance and growth of specific neuronal populations, whereas its precursor, proNGF, is involved in neuronal apoptosis. Binding of NGF or proNGF to TrkA, p75<sup>NTR</sup> , and VP10p receptors triggers complex intracellular signaling pathways that can be modulated by endogenous small-molecule ligands. Here, we show by isothermal titration calorimetry and NMR that ATP binds to the intrinsically disordered pro-  ...[more]

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