3ALP

Cell adhesion protein

Summary for 3ALP

• Entry DOI: 10.2210/pdb3alp/pdb
• Descriptor: Poliovirus receptor-related protein 1, CITRIC ACID, HEXANE-1,6-DIOL, ... (4 entities in total)
• Functional Keywords: immunoglobulin-like domain, v-set, c2-set, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Alpha: Cell membrane; Single-pass type I membrane protein. Isoform Delta: Cell membrane; Single-pass type I membrane protein. Isoform Gamma: Secreted: Q15223
• Total number of polymer chains: 2
• Total formula weight: 74379.41

Authors

Narita, H.,Nakagawa, A.,Suzuki, M. (deposition date: 2010-08-05, release date: 2011-02-16, Last modification date: 2017-10-11)

Primary citation

Narita, H.,Yamamoto, Y.,Suzuki, M.,Miyazaki, N.,Yoshida, A.,Kawai, K.,Iwasaki, K.,Nakagawa, A.,Takai, Y.,Sakisaka, T.
Crystal Structure of the cis-Dimer of Nectin-1: implications for the architecture of cell-cell junctions
J.Biol.Chem., 286:12659-12669, 2011

PubMed Abstract: In 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.

PubMed: 21325282
DOI: 10.1074/jbc.M110.197368

Experimental method

X-RAY DIFFRACTION (2.804 Å)