Structural insights into the contactin 1 - neurofascin 155 adhesion complex

DOI: 10.1038/s41467-022-34302-9

Authors: Lucas M. P. Chataigner (Utrecht University) , Christos Gogou (Delft University of Technology) , Maurits A. Den Boer (Utrecht University; Netherlands Proteomics Center) , Cátia P. Frias (Delft University of Technology) , Dominique M. E. Thies-Weesie (Utrecht University) , Joke C. M. Granneman (Utrecht University) , Albert J. R. Heck (Utrecht University; Netherlands Proteomics Center) , Dimphna H. Meijer (Delft University of Technology) , Bert J. C. Janssen (Utrecht University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 13

State: Published (Approved)
Published: November 2022
Diamond Proposal Number(s): 19800

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.

Journal Keywords: Cell adhesion; Glycosylation; X-ray crystallography

Subject Areas: Biology and Bio-materials, Medicine


Instruments: B21-High Throughput SAXS , I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 09/11/2022 09:22

Documents:
s41467-022-34302-9.pdf

Discipline Tags:

Neurodegenerative Diseases Non-Communicable Diseases Health & Wellbeing Neurology Structural biology Biophysics Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Scattering Macromolecular Crystallography (MX) Small Angle X-ray Scattering (SAXS)