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Structure. 2019 Jun 4;27(6):893-906.e9. doi: 10.1016/j.str.2019.03.004. Epub 2019 Apr 4.

A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse.

Author information

1
Child Health Institute of New Jersey, New Brunswick, NJ 08901, USA.
2
Department of Biology and Biotechnology "Charles Darwin" and Pasteur Institute - Cenci Bolognetti Foundation, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
3
Department of Molecular Biology and Biochemistry and Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
4
Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada.
5
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
6
Department of Molecular Biology and Biochemistry and Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
7
Child Health Institute of New Jersey, New Brunswick, NJ 08901, USA; Departments of Neuroscience and Cell Biology Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA; Department of Pediatrics, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA; School of Biological Sciences, Victoria University of Wellington, Wellington 6140, New Zealand. Electronic address: comoleda@rwjms.rutgers.edu.

Abstract

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.

KEYWORDS:

ELISA; IgLON; SAXS; ligand-receptor pair; protein crystallography

PMID:
30956130
PMCID:
PMC6609445
[Available on 2020-06-04]
DOI:
10.1016/j.str.2019.03.004

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