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J Biol Chem. 2017 Oct 6;292(40):16477-16490. doi: 10.1074/jbc.M117.795567. Epub 2017 Aug 25.

Cell-cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin-binding interface.

Author information

From the Program in Genetics.
Department of Zoology, and.
the Departments of Biological Sciences and.
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706.
Chemistry, Seoul National University, Seoul 08826, South Korea, and.
the Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305.
From the Program in Genetics,


Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalian α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly in vitro and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 Ser-47 and Tyr-69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40-100-fold in vitro. In vivo experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formation in C. elegans Our data provide novel insights into how cadherin-dependent cell-cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.


adherens junction; cadherin-catenin complex; crystal structure; morphogenesis; phosphoregulation; α-catenin; β-catenin

[Available on 2018-10-06]
[Indexed for MEDLINE]

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