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

Fanomezana M. Ranaivoson, Liam S. Turk, Sinem Ozgul, Sumie Kakehi, Sventja von Daake, Nicole Lopez, Laura Trobiani, Antonella De Jaco, Natalia Denissova, Borries Demeler, Engin Özkan, Gaetano Montelione, Davide Comoletti

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 Taken together, we report 89 unpublished cell-surface ligand-receptor pairs and describe structural models of trans interactions of IgLONs, showing that their structures are compatible with a model of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. 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.

Original languageEnglish (US)
Pages (from-to)893-906.e9
JournalStructure
Volume27
Issue number6
DOIs
StatePublished - Jun 4 2019

Fingerprint

Proteomics
Synapses
Proteins
Membrane Proteins
Protein Interaction Maps
Cell Aggregation
Structural Models
Membrane Glycoproteins
Cell Surface Receptors
Dimerization
Growth
Adhesives
Immunoglobulins
Ligands
Brain
neurotrimin

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

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

Cite this

Ranaivoson, Fanomezana M. ; Turk, Liam S. ; Ozgul, Sinem ; Kakehi, Sumie ; von Daake, Sventja ; Lopez, Nicole ; Trobiani, Laura ; De Jaco, Antonella ; Denissova, Natalia ; Demeler, Borries ; Özkan, Engin ; Montelione, Gaetano ; Comoletti, Davide. / A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse. In: Structure. 2019 ; Vol. 27, No. 6. pp. 893-906.e9.
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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. 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.",
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author = "Ranaivoson, {Fanomezana M.} and Turk, {Liam S.} and Sinem Ozgul and Sumie Kakehi and {von Daake}, Sventja and Nicole Lopez and Laura Trobiani and {De Jaco}, Antonella and Natalia Denissova and Borries Demeler and Engin {\"O}zkan and Gaetano Montelione and Davide Comoletti",
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Ranaivoson, FM, Turk, LS, Ozgul, S, Kakehi, S, von Daake, S, Lopez, N, Trobiani, L, De Jaco, A, Denissova, N, Demeler, B, Özkan, E, Montelione, G & Comoletti, D 2019, 'A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse', Structure, vol. 27, no. 6, pp. 893-906.e9. https://doi.org/10.1016/j.str.2019.03.004

A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse. / Ranaivoson, Fanomezana M.; Turk, Liam S.; Ozgul, Sinem; Kakehi, Sumie; von Daake, Sventja; Lopez, Nicole; Trobiani, Laura; De Jaco, Antonella; Denissova, Natalia; Demeler, Borries; Özkan, Engin; Montelione, Gaetano; Comoletti, Davide.

In: Structure, Vol. 27, No. 6, 04.06.2019, p. 893-906.e9.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse

AU - Ranaivoson, Fanomezana M.

AU - Turk, Liam S.

AU - Ozgul, Sinem

AU - Kakehi, Sumie

AU - von Daake, Sventja

AU - Lopez, Nicole

AU - Trobiani, Laura

AU - De Jaco, Antonella

AU - Denissova, Natalia

AU - Demeler, Borries

AU - Özkan, Engin

AU - Montelione, Gaetano

AU - Comoletti, Davide

PY - 2019/6/4

Y1 - 2019/6/4

N2 - 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. 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.

AB - 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. 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.

KW - ELISA

KW - IgLON

KW - SAXS

KW - ligand-receptor pair

KW - protein crystallography

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