Effects of ATP binding on the conformational flexibility of proNGF

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.