Engineering β-catenin-derived peptides for α-catenin binding
<p dir="ltr">The complex formed by the β-catenin and α-catenin adaptor proteins acts as a molecular bridge that enables E-cadherin-based cell–cell adhesion assembly and maintenance in the epithelial tissue. This occurs through the interaction between the intracellular domain of E-cad...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , |
| منشور في: |
2024
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| الملخص: | <p dir="ltr">The complex formed by the β-catenin and α-catenin adaptor proteins acts as a molecular bridge that enables E-cadherin-based cell–cell adhesion assembly and maintenance in the epithelial tissue. This occurs through the interaction between the intracellular domain of E-cadherin and β-catenin on the one hand and between F-actin and α-catenin on the other hand. In addition to its role in cell–cell adhesion formation, it has been reported that E-cadherin mediates breast cancer cell metastasis to distant organs. Therefore, development of biomaterials such as peptides with ability to modulate the interaction between β-catenin and α-catenin presents an opportunity to modulate cell–cell adhesion. Here, we have performed computational and experimental analysis to develop β-catenin-derived peptides with the ability to bind α-catenin. Specifically, we analyzed the available β- and α-catenin complex structure and identified residues on β-catenin having potential to form new interactions upon mutation. We tested the wild-type (WT) and mutant β-catenin-derived peptides for their binding to α-catenin using conventional and steered molecular dynamics simulations, revealing an increased interaction of P128E and M131E mutant peptides. We then designed a Bioluminescence Resonance Energy Transfer (BRET)-based assay to monitor binding of the β-catenin-derived peptides with α-catenin, which revealed similar binding affinities of the WT and mutant β-catenin-derived peptides. Further, expression of the WT and the M131E mutant peptide resulted in a change in the aspect ratio of the cells suggestive of their ability to affect cell–cell adhesion. We envisage that the β-catenin-derived peptides engineered here will find application in blocking the interaction between β-catenin and α-catenin and, thus, modulate E-cadherin adhesion, which may lead to potential therapeutic avenue in abrogating E-cadherin-mediated metastasis of invasive breast cancer cells.</p><h2>Other Information</h2><p dir="ltr">Published in: Emergent Materials<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s42247-024-00663-8" target="_blank">https://dx.doi.org/10.1007/s42247-024-00663-8</a></p> |
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