Nectin ectodomain structures reveal a canonical adhesive interface

Oliver J. Harrison, Jeremie Vendome, Julia Brasch, Xiangshu Jin, Soonjin Hong, Phinikoula S. Katsamba, Goran Ahlsen, Regina B. Troyanovsky, Sergey M Troyanovsky, Barry Honig*, Lawrence Shapiro

*Corresponding author for this work

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)906-915
Number of pages10
JournalNature Structural and Molecular Biology
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2012

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Harrison, O. J., Vendome, J., Brasch, J., Jin, X., Hong, S., Katsamba, P. S., Ahlsen, G., Troyanovsky, R. B., Troyanovsky, S. M., Honig, B., & Shapiro, L. (2012). Nectin ectodomain structures reveal a canonical adhesive interface. Nature Structural and Molecular Biology, 19(9), 906-915. https://doi.org/10.1038/nsmb.2366