Abstract
Contactin-2 (CNTN2), an immunoglobulin cell adhesion molecule (IgCAM) expressed on the neural cell surface, regulates the formation of myelin sheaths, facilitates communication between neurons and axoglial cells, and coordinates the migration of neural cells. However, the assembly of full-length CNTN2 is still not fully elucidated. Here, we found that the full-length human CNTN2 forms a concentration-dependent homodimer. We further determined the cryo-EM structures of the full-length CNTN2, revealing a novel bowknot-shaped scaffold constituted of the Ig1-6 repeats from two protomers, with the flexible ribbon-like FNIII repeats extending outward in opposite directions. The Ig1-6 domains, rather than the previously proposed Ig1-4 domains, have an indispensable role in mediating CNTN2-dependent cell adhesion and clustering. Moreover, structure-guided mutagenesis analyses supported the idea that CNTN2 homodimerization observed in our structure is essential for cell adhesion. Our findings offer novel insights into the mechanism through which CNTN2 forms a homodimer to maintain cell-cell contacts in the nervous system.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callSimilar Papers
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
