Nectin ectodomain structures reveal a canonical adhesive interface

• Published in: Nature structural & molecular biology Vol. 19; no. 9; pp. 906 - 915
• Main Authors: Harrison, Oliver J, Vendome, Jeremie, Brasch, Julia, Jin, Xiangshu, Hong, Soonjin, Katsamba, Phinikoula S, Ahlsen, Goran, Troyanovsky, Regina B, Troyanovsky, Sergey M, Honig, Barry, Shapiro, Lawrence
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2012; Nature Publishing Group
• Subjects: 631/45/535; 631/45/612/1231; Adhesion; Adhesives; Animals; Antigens, Neoplasm - metabolism; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Cell Adhesion; Cell adhesion & migration; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - metabolism; Cell Line; Crystal structure; Crystallography, X-Ray; Glycoproteins; Health aspects; Humans; Life Sciences; Membrane Biology; Mice; Models, Molecular; Molecular biology; Nectins; Neoplasm Proteins - metabolism; Physiological aspects; Protein Binding; Protein Multimerization; Protein Structure; Protein Structure, Tertiary; Receptors, Virus - metabolism; Vertebrates; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.2366

Nectins and nectin-like proteins promote intercellular adhesion and tissue patterning in vertebrates through homophilic or heterophilic interactions. Now the formation of all the possible nectin pairs is studied systematically in vitro , and crystal structures provide insight into the molecular basis for the adhesive binding specificity of nectins. Nectins are immunoglobulin superfamily glycoproteins that mediate intercellular adhesion in many vertebrate tissues. Homophilic and heterophilic interactions between nectin family members help mediate tissue patterning. We determined the homophilic binding affinities and heterophilic specificities of all four nectins and the related protein nectin-like 5 (Necl-5) from human and mouse, revealing a range of homophilic interaction strengths and a defined heterophilic specificity pattern. To understand the molecular basis of their adhesion and specificity, we determined the crystal structures of natively glycosylated full ectodomains or adhesive fragments of all four nectins and Necl-5. All of the crystal structures revealed dimeric nectins bound through a stereotyped interface that was previously proposed to represent a cis dimer. However, conservation of this interface and the results of targeted cross-linking experiments showed that this dimer probably represents the adhesive trans interaction. The structure of the dimer provides a simple molecular explanation for the adhesive binding specificity of nectins.