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Download fileA Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse
journal contribution
posted on 04.08.2022, 22:22 authored by FM Ranaivoson, LS Turk, S Ozgul, S Kakehi, S von Daake, N Lopez, L Trobiani, A De Jaco, N Denissova, B Demeler, E Özkan, GT Montelione, Davide ComolettiDavide ComolettiIn 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 Taken together, we report 89 unpublished cell-surface ligand-receptor pairs and describe structural models of trans interactions of IgLONs, showing that their structures are compatible with a model of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. Many aspects of synapse formation, specification, and maturation rely on interactions among a rich repertoire of cell-surface glycoproteins with adhesive and repulsive properties. Although the identity of these proteins is known, their network of interactions remains largely untapped. Ranaivoson et al. have identified a number of protein-protein interactions and have determined the structures of three members of the IgLONs, a family of five proteins of the immunoglobulin superfamily that has recently been implicated in a wide range of human disease.
Funding
Collaborative Research: Structure and Function of Reelin in Brain Development | Funder: RUTGERS UNIVERSITY | Grant ID: 1755189
History
Preferred citation
Ranaivoson, F. M., Turk, L. S., Ozgul, S., Kakehi, S., von Daake, S., Lopez, N., Trobiani, L., De Jaco, A., Denissova, N., Demeler, B., Özkan, E., Montelione, G. T. & Comoletti, D. (2019). A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse. Structure, 27(6), 893-906.e9. https://doi.org/10.1016/j.str.2019.03.004Publisher DOI
Journal title
StructureVolume
27Issue
6Publication date
04/06/2019Pagination
893-906.e9Publisher
Elsevier BVPublication status
PublishedOnline publication date
04/04/2019ISSN
0969-2126eISSN
1878-4186Language
enUsage metrics
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Categories
Keywords
ELISAIgLONSAXSligand-receptor pairprotein crystallographyAmino Acid SequenceAnimalsBrainCell Adhesion Molecules, NeuronalGPI-Linked ProteinsHumansLigandsModels, MolecularNeural Cell Adhesion MoleculesProtein BindingProtein ConformationProtein MultimerizationProteomicsSequence Homology, Amino AcidSynapsesNeurosciencesRare Diseases2 Aetiology1 Underpinning research1.1 Normal biological development and functioning2.1 Biological and endogenous factorsGeneric health relevanceChemical SciencesBiological SciencesInformation and Computing SciencesBiophysics