title: Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell-cell adhesion.
abstract: Nectins are members of the Ig superfamily that mediate cell-cell adhesion through homophilic and heterophilic interactions. We have determined the crystal structure of the nectin-2 homodimer at 1.3 Å resolution. Structural analysis and complementary mutagenesis studies reveal the basis for recognition and selectivity among the nectin family members. Notably, the close proximity of charged residues at the dimer interface is a major determinant of the binding affinities associated with homophilic and heterophilic interactions within the nectin family. Our structural and biochemical data provide a mechanistic basis to explain stronger heterophilic versus weaker homophilic interactions among these family members and also offer insights into nectin-mediated transinteractions between engaging cells.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Samanta
authors.forename: Udupi A
authors.initials: UA
authors.lastname: Ramagopal
authors.forename: Rotem
authors.initials: R
authors.lastname: Rubinstein
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vigdorovich
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
mesh_terms: D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D000075983:Nectins; D011485:Protein Binding; D060066:Protein Interaction Maps; D017422:Sequence Analysis, DNA
chemical_list: D015815:Cell Adhesion Molecules; D000075983:Nectins