Structural insights into the contactin 1 - neurofascin 155 adhesion complex

Nat Commun. 2022 Nov 3;13(1):6607. doi: 10.1038/s41467-022-34302-9.

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 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.

MeSH terms

  • Axons / metabolism
  • Cell Adhesion Molecules* / metabolism
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Contactin 1*
  • Contactins
  • Nerve Growth Factors / metabolism

Substances

  • Contactin 1
  • Cell Adhesion Molecules
  • Nerve Growth Factors
  • Contactins
  • Cell Adhesion Molecules, Neuronal