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Endogenous modulators of neurotrophin signaling: Landscape of the transient ATP-NGF interactions
oleh: Francesca Paoletti, Franci Merzel, Alberto Cassetta, Iza Ogris, Sonia Covaceuszach, Jože Grdadolnik, Doriano Lamba, Simona Golič Grdadolnik
Format: | Article |
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Diterbitkan: | Elsevier 2021-01-01 |
Deskripsi
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 p75NTR 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.