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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...

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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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Related Experiment Video

Updated: Jun 17, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Published on: October 17, 2014

Distal interactions within the par3-VE-cadherin complex.

Robert C Tyler¹, Francis C Peterson, Brian F Volkman

¹Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

|January 6, 2010

Summary

Par3 scaffold protein uses dual binding modes to interact with VE-Cad, crucial for endothelial cell polarity. Phosphorylation enhances this interaction, revealing a mechanism for specificity in cell polarity networks.

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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

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Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands

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In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Area of Science:

Cell Biology
Molecular Biology
Structural Biology

Background:

Par3 is a scaffold protein organizing cell polarity complexes with par6 and aPKC.
Par3's PDZ domains target plasma membrane proteins, regulating epithelial cell polarity.
The interaction of par3-PDZ3 with VE-Cad suggests a role in endothelial cell polarity, but details are unknown.

Purpose of the Study:

To elucidate the molecular details of the par3-PDZ3 and VE-Cad interaction.
To determine if par3-PDZ3 utilizes both canonical and distal binding modes with VE-Cad.
To understand the mechanism of ligand specificity within the cell polarity network.

Main Methods:

Determined the crystal structure of par3-PDZ3 bound to the VE-Cad C-terminal tail.
Employed biophysical measurements including fluorescence polarization and 2D NMR.
Investigated the effect of VE-Cad phosphorylation on par3 binding affinity.

Main Results:

The structure reveals that par3-PDZ3 utilizes both canonical and distal binding modes with VE-Cad.
Intermolecular charge pairing between Asp777 (VE-Cad) and Arg609 (par3-PDZ3) is critical for complex formation.
Phosphorylation of VE-Cad at Ser776 significantly increases its affinity for par3.

Conclusions:

Par3-PDZ3 exhibits dual-class specificity by accommodating both canonical and distal interaction modes.
VE-Cad phosphorylation enhances par3 binding, demonstrating a role for post-translational modifications in PDZ-ligand interactions.
These findings provide insight into the molecular mechanisms governing endothelial cell polarity.