A proteomic screen of neuronal cell-surface molecules reveals IgLONs as structurally conserved interaction modules at the synapse
Ranaivoson, Fanomezana M.
Turk, Liam S.
von Daake, Sventja
De Jaco, Antonella
In the developing brain, cell-surface proteins play crucial roles, but their protein-protein interaction network remains largely unknown. A proteomic screen identified 200 interactions, 89 of which were not previously published. Among these interactions, we find that the IgLONs, a family of five cell-surface neuronal proteins implicated in various human disorders, interact as homo- and heterodimers. We reveal their interaction patterns and report the dimeric crystal structures of Neurotrimin (NTRI), IgLON5, and the neuronal growth regulator 1 (NEGR1)/IgLON5 complex. We show that IgLONs maintain an extended conformation and that their dimerization occurs through the first Ig domain of each monomer and is Ca2+ independent. Cell aggregation shows that NTRI and NEGR1 homo- and heterodimerize in trans. Taken together, we report 89 unpublished cell-surface ligand-receptor pairs and describe structural models of trans interactions of IgLONs, showing that their structures are compatible with a model of interaction across the synaptic cleft.
Accepted author manuscript
Ligand-receptor pair , ELISA , IgLON , Protein crystallography , SAXS , Cell-surface
Ranaivoson, F. M., Turk, L. S., Ozgul, S., Kakehi, S., von Daake, S., Lopez, N., Trobiani, L., De Jaco, A., Denissova, N., Demeler, B., Özcan, E., Montelione, G. T., & Comoletti, D. (2019). A proteomic screen of neuronal cell-surface molecules reveals IgLONs as structurally conserved interaction molecules at the synapse. Structure, 27(6), 893-906. https://doi.org/10.1016/j.str.2019.03.004