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Endogenous modulators of neurotrophin signaling: Landscape of the transient ATP-NGF interactions.

ABSTRACT: The Nerve Growth Factor (NGF) neurotrophin acts in the maintenance and growth of neuronal populations. Despite the detailed knowledge of NGF's role in neuron physiology, the structural and mechanistic determinants of NGF bioactivity modulated by essential endogenous ligands are still lacking. We present the results of an integrated structural and advanced computational approach to characterize the extracellular ATP-NGF interaction. We mapped by NMR the interacting surface and ATP orientation on NGF and revealed the functional role of this interaction in the binding to TrkA and p75^NTR receptors by SPR. The role of divalent ions was explored in conjunction with ATP. Our results pinpoint ATP as a likely transient molecular modulator of NGF signaling, in health and disease states.

SUBMITTER: Paoletti F

PROVIDER: S-EPMC8164016 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Endogenous modulators of neurotrophin signaling: Landscape of the transient ATP-NGF interactions.

Paoletti Francesca F Merzel Franci F Cassetta Alberto A Ogris Iza I Covaceuszach Sonia S Grdadolnik Jože J Lamba Doriano D Golič Grdadolnik Simona S

Computational and structural biotechnology journal 20210507

The Nerve Growth Factor (NGF) neurotrophin acts in the maintenance and growth of neuronal populations. Despite the detailed knowledge of NGF's role in neuron physiology, the structural and mechanistic determinants of NGF bioactivity modulated by essential endogenous ligands are still lacking. We present the results of an integrated structural and advanced computational approach to characterize the extracellular ATP-NGF interaction. We mapped by NMR the interacting surface and ATP orientation on ...[more]

PMID: 34136093

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