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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.

SUBMITTER: Samanta D

PROVIDER: S-EPMC3443150 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell-cell adhesion.

Samanta Dibyendu D Ramagopal Udupi A UA Rubinstein Rotem R Vigdorovich Vladimir V Nathenson Stanley G SG Almo Steven C SC

Proceedings of the National Academy of Sciences of the United States of America 20120827 37

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 ...[more]

PMID: 22927415

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