Structural insights into the contactin 1 - neurofascin 155 adhesion complex
Chataigner, Lucas M P; Gogou, Christos; den Boer, Maurits A; Frias, Cátia P; Thies-Weesie, Dominique M E; Granneman, Joke C M; Heck, Albert J R; Meijer, Dimphna H; Janssen, Bert J C
(2022) Nature Communications, volume 13, issue 1
(Article)
Abstract
Cell-surface expressed contactin 1 and neurofascin 155 control wiring of the nervous system and interact across cells to form and maintain paranodal myelin-axon junctions. The molecular mechanism of contactin 1 - neurofascin 155 adhesion complex formation is unresolved. Crystallographic structures of complexed and individual contactin 1 and neurofascin 155 binding
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regions presented here, provide a rich picture of how competing and complementary interfaces, post-translational glycosylation, splice differences and structural plasticity enable formation of diverse adhesion sites. Structural, biophysical, and cell-clustering analysis reveal how conserved Ig1-2 interfaces form competing heterophilic contactin 1 - neurofascin 155 and homophilic neurofascin 155 complexes whereas contactin 1 forms low-affinity clusters through interfaces on Ig3-6. The structures explain how the heterophilic Ig1-Ig4 horseshoe's in the contactin 1 - neurofascin 155 complex define the 7.4 nm paranodal spacing and how the remaining six domains enable bridging of distinct intercellular distances.
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Keywords: Contactin 1, Cell Adhesion Molecules/metabolism, Nerve Growth Factors/metabolism, Contactins, Axons/metabolism, Cell Adhesion Molecules, Neuronal/metabolism
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: We thank the staff of the DLS beamlines I03 and I24 for help with X-ray diffraction data collection and of beamline B21 for help with SAXS data collection. L.M.P.C. thanks Nick Pearce, Jitse van der Horn, and Gijs van der Schot, for the instructional conversations regarding crystallography. K562 cells were a kind gift from Dr. Bas van Steensel at Netherlands Cancer Institute. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program with grant agreement No. 677500 (to B.J.C.J.). D.H.M. acknowledges support from Parents in KIND grant, sponsored by the Kavli Institute of Nanoscience, the Department of Bionanoscience in Delft, and the NWO Spinoza Prize. M.A.d.B. and A.J.R.H. acknowledge support from the Netherlands Organization for Scientific Research (NWO) funding the Netherlands Proteomics Centre through the X-omics Road Map program (project 184.034.019). Funding Information: We thank the staff of the DLS beamlines I03 and I24 for help with X-ray diffraction data collection and of beamline B21 for help with SAXS data collection. L.M.P.C. thanks Nick Pearce, Jitse van der Horn, and Gijs van der Schot, for the instructional conversations regarding crystallography. K562 cells were a kind gift from Dr. Bas van Steensel at Netherlands Cancer Institute. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program with grant agreement No. 677500 (to B.J.C.J.). D.H.M. acknowledges support from Parents in KIND grant, sponsored by the Kavli Institute of Nanoscience, the Department of Bionanoscience in Delft, and the NWO Spinoza Prize. M.A.d.B. and A.J.R.H. acknowledge support from the Netherlands Organization for Scientific Research (NWO) funding the Netherlands Proteomics Centre through the X-omics Road Map program (project 184.034.019). Publisher Copyright: © 2022, The Author(s).
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