| First Author | Liu X | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 6 | Pages | 2068-2077 |
| PubMed ID | 30674679 | Mgi Jnum | J:271113 |
| Mgi Id | MGI:6278436 | Doi | 10.1073/pnas.1810969116 |
| Citation | Liu X, et al. (2019) Structure of the heterophilic interaction between the nectin-like 4 and nectin-like 1 molecules. Proc Natl Acad Sci U S A 116(6):2068-2077 |
| abstractText | Nectin-like (Necl) molecules are Ca(2+)-independent Ig-like transmembrane cell adhesion molecules that participate in junctions between different cell types. The specific cell-cell adhesions mediated by Necl proteins are important in neural development and have been implicated in neurodegenerative diseases. Here, we present the crystal structure of the mouse Necl-4 full ectodomain and the structure of the heterophilic Necl ectodomain complex formed by the mNecl-4 and mNecl-1 ectodomains. We demonstrate that, while the ectodomain of mNecl-4 is monomeric, it forms a stable heterodimer with Ig1 of mNecl-1, with an affinity significantly higher than that observed for self-dimerization of the mNecl-1 ectodomain. We validated our structural characterizations by performing a surface plasmon resonance assay and an Fc fusion protein binding assay in mouse primary dorsal root ganglia neurites and Schwann cells and identified a selection of residues important for heterophilic interactions. Finally, we proposed a model of Necl binding specificity that involves an induced-fit conformational change at the dimerization interface. |
