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Highlights • Sortilin binds ligands via two binding sites inside the β-propeller cavity • Protein and peptide ligands have distinct impacts on sortilin conformation • Only protein ligands induce stabilization in the membrane-proximal 10CC domains • HDX-MS reveals how diverse biological functions of sortilin may be mediated Summary Sortilin is a multifunctional neuronal receptor involved in sorting of neurotrophic factors and apoptosis signaling.
Nerve growth factor-? (NGF) is essential for the correct development of the nervous system. NGF exists in both a mature form and a pro-form (proNGF). The two forms have opposing effects on neurons: NGF induces proliferation, whereas proNGF induces apoptosis via binding to a receptor complex of the common neurotrophin receptor (p75NTR) and sortilin. The overexpression of both proNGF and sortilin has been associated with several neurodegenerative diseases.
Nerve growth factor-? (NGF) is essential for correct development of the nervous system. NGF exists both in a mature and a pro-form (proNGF). The two forms have opposing effects on neurons, in which NGF induces proliferation, while proNGF induces apoptosis via binding to a receptor complex of the common neurotrophine receptor (p75NTR) and Sortilin. Overexpression of both proNGF and Sortilin has been associated with several neurodegenerative diseases.
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