TY - JOUR
T1 - Structure of nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell-cell adhesion
AU - Samanta, Dibyendu
AU - Ramagopal, Udupi A.
AU - Rubinstein, Rotem
AU - Vigdorovich, Vladimir
AU - Nathenson, Stanley G.
AU - Almo, Steven C.
PY - 2012/9/11
Y1 - 2012/9/11
N2 - 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.
AB - 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.
KW - Cell adhesion molecule
KW - Immunoglobulin superfamily
KW - Nectin-2 dimer
KW - X-ray crystallography
UR - http://www.scopus.com/inward/record.url?scp=84866274323&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866274323&partnerID=8YFLogxK
U2 - 10.1073/pnas.1212912109
DO - 10.1073/pnas.1212912109
M3 - Article
C2 - 22927415
AN - SCOPUS:84866274323
SN - 0027-8424
VL - 109
SP - 14836
EP - 14840
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 37
ER -