3alp | pdb_00003alp
Cell adhesion protein
Structural highlights
Disease[PVRL1_HUMAN] Zlotogora-Ogur syndrome;Cleft lip with or without cleft palate. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[PVRL1_HUMAN] Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions have been detected between PVRL1/nectin-1 and PVRL3/nectin-3 and between PVRL1/nectin-1 and PVRL4/nectin-4. Functions as an entry receptor for herpes simplex virus and pseudorabies virus.[1] Publication Abstract from PubMedIn multicellular organisms, cells are interconnected by cell adhesion molecules. Nectins are immunoglobulin (Ig)-like cell adhesion molecules that mediate homotypic and heterotypic cell-cell adhesion, playing key roles in tissue organization. To mediate cell-cell adhesion, nectin molecules dimerize in cis on the surface of the same cell, followed by trans-dimerization of the cis-dimers between the neighboring cells. Previous cell biological studies deduced that the first Ig-like domain of nectin and the second Ig-like domain are involved in trans-dimerization and cis-dimerization, respectively. However, to understand better the steps involved in nectin adhesion, the structural basis for the dimerization of nectin must be determined. In this study, we determined the first crystal structure of the entire extracellular region of nectin-1. In the crystal, nectin-1 formed a V-shaped homophilic dimer through the first Ig-like domain. Structure-based site-directed mutagenesis of the first Ig-like domain identified four essential residues that are involved in the homophilic dimerization. Upon mutating the four residues, nectin-1 significantly decreased cis-dimerization on the surface of cultured cells and abolished the homophilic and heterophilic adhesion activities. These results indicate that, in contrast with the previous notion, our structure represents a cis-dimer. Thus, our findings clearly reveal the structural basis for the cis-dimerization of nectins through the first Ig-like domains. Crystal Structure of the cis-Dimer of Nectin-1: implications for the architecture of cell-cell junctions.,Narita H, Yamamoto Y, Suzuki M, Miyazaki N, Yoshida A, Kawai K, Iwasaki K, Nakagawa A, Takai Y, Sakisaka T J Biol Chem. 2011 Apr 8;286(14):12659-69. Epub 2011 Feb 15. PMID:21325282[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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