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, 2019 02 05.
Article
in En
| MEDLINE
| ID: mdl-30674679
ABSTRACT
Nectin-like (Necl) molecules are Ca2+-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulins
/
Cell Adhesion Molecules
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2019
Type:
Article