TY - JOUR
T1 - Structural insights into the contactin 1 – neurofascin 155 adhesion complex
AU - Chataigner, Lucas M.P.
AU - Gogou, Christos
AU - den Boer, Maurits A.
AU - Frias, Cátia P.
AU - Thies-Weesie, Dominique M.E.
AU - Granneman, Joke C.M.
AU - Heck, Albert J.R.
AU - Meijer, Dimphna H.
AU - Janssen, Bert J.C.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141201941&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-34302-9
DO - 10.1038/s41467-022-34302-9
M3 - Article
C2 - 36329006
AN - SCOPUS:85141201941
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6607
ER -