5xa5

Publication Abstract from PubMed

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 alpha- and beta-catenin. HMP-1, unlike its mammalian homolog alpha-catenin, is constitutively monomeric, and its binding affinity for HMP-2/beta-catenin is higher than that of alpha-catenin for beta-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 alpha-catenin.beta-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.

Cell-cell adhesion in metazoans relies on evolutionarily conserved features of the alpha-catenin.beta-catenin-binding interface.,Shao X, Kang H, Loveless T, Lee GR, Seok C, Weis WI, Choi HJ, Hardin J J Biol Chem. 2017 Oct 6;292(40):16477-16490. doi: 10.1074/jbc.M117.795567. Epub, 2017 Aug 25. PMID:28842483^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.