Solution Structure of the Epithelial Cadherin Domain Responsible for Selective Cell Adhesion

Overduin, Michael; Harvey, Timothy S.; Bagby, Stefan; Tong, Kit I.; Yau, Patrick; Takeichi, Masatoshi; Ikura, Mitsuhiko

doi:10.1126/science.7824937

Cited by 401 publications

(298 citation statements)

References 26 publications

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“…The members are called E-cadherin (cdh1), N-cadherin (cdh2), and so on, each of which shows a distinct tissue distribution pattern (Takeichi 1988). Their extracellular domain is divided into five repetitive subdomains, called cadherin repeats or EC domains, and each subdomain contains calcium-binding sequences (Overduin et al 1995). The interaction of calcium ions with these sequences controls the conformation of the extracellular domain (Pokutta et al 1994), switching its adhesive function "off " and "on."…”

Section: Cadherinsmentioning

confidence: 99%

Adherens Junction: Molecular Architecture and Regulation

Meng¹,

Takeichi²

2009

Cold Spring Harbor Perspectives in Biology

509

449

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Section: Cadherinsmentioning

confidence: 99%

Adherens Junction: Molecular Architecture and Regulation

Meng¹,

Takeichi²

2009

Cold Spring Harbor Perspectives in Biology

509

449

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“…The three-dimensional structures of a number of type I and type II cadherin ectodomain adhesive regions have been determined by both X-ray crystallography and NMR, and the structure for the full ectodomain of Xenopus laevis C-cadherin has also been determined [13][14][15][16][17][18][19][20][21][22][23] . Table 1 contains a list of all available cadherin structures 13-25 .…”

Section: Introductionmentioning

confidence: 99%

Sequence and Structural Determinants of Strand Swapping in Cadherin Domains: Do All Cadherins Bind Through the Same Adhesive Interface?

Posy

Shapiro

Honig

2008

Journal of Molecular Biology

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SUMMARYCadherins are cell surface adhesion proteins important for tissue development and integrity. Type I and type II, or "classical", cadherins form adhesive dimers via an interface formed through the exchange, or "swapping", of the N-terminal β-strands from their membrane-distal EC1 domains. Here we ask which sequence and structural features in EC1 domains are responsible for β-strand swapping and whether members of other cadherin families also form similar strand-swapped binding interfaces. We first create a comprehensive database consisting of multiple alignments of each type of cadherin domain. We use the known three-dimensional structures of classical cadherins to identify conserved positions in multiple sequence alignments that appear to be crucial determinants of the cadherin domain structure. We further identify features that are unique to EC1 domains. On the basis of our analysis we conclude that all cadherin domains have very similar overall folds but, with the exception of classical and desmosomal cadherin EC1 domains, most of them do not appear to bind through a strand swapping mechanism. Thus, non-classical cadherins that function in adhesion are likely to use different protein-protein interaction interfaces. Our results have implications for the evolution of molecular mechanisms of cadherin-mediated adhesion in vertebrates.

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“…E-cadherin (E-cad) is a transmembrane glycoprotein normally expressed in the plasma membranes of epithelial cells, in which it mediates homophilic, Ca 2+ -dependent intercellular adhesion in adherens junctions (1). It interacts with the intracellular a, h, and g catenins (2) and, through those molecules, is connected to the actin cytoskeleton.…”

Section: Introductionmentioning

confidence: 99%

Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells

Reinhold

Reimers

Maunakea

et al. 2007

Molecular Cancer Therapeutics

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E-cadherin (E-cad) is a transmembrane adhesion glycoprotein, the expression of which is often reduced in invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfitesequencing for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically significant levels. Above a threshold of f20% to 30% mean methylation, the expression of E-cad was effectively silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other cancer-related genes. As has been shown

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Solution Structure of the Epithelial Cadherin Domain Responsible for Selective Cell Adhesion

Cited by 401 publications

References 26 publications

Adherens Junction: Molecular Architecture and Regulation

Adherens Junction: Molecular Architecture and Regulation

Sequence and Structural Determinants of Strand Swapping in Cadherin Domains: Do All Cadherins Bind Through the Same Adhesive Interface?

Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells

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