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:
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| مؤلفون آخرون: | , , , |
| منشور في: |
2024
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إضافة وسم
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| _version_ | 1864513510329810944 |
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| author | S. M. Nasir Uddin (19198030) |
| author2 | Saad Rasool (9764093) Anupriya M. Geethakumari (17052375) Wesam S. Ahmed (10170053) Kabir H. Biswas (5705864) |
| author2_role | author author author author |
| author_facet | S. M. Nasir Uddin (19198030) Saad Rasool (9764093) Anupriya M. Geethakumari (17052375) Wesam S. Ahmed (10170053) Kabir H. Biswas (5705864) |
| author_role | author |
| dc.creator.none.fl_str_mv | S. M. Nasir Uddin (19198030) Saad Rasool (9764093) Anupriya M. Geethakumari (17052375) Wesam S. Ahmed (10170053) Kabir H. Biswas (5705864) |
| dc.date.none.fl_str_mv | 2024-03-06T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s42247-024-00663-8 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Engineering_-catenin-derived_peptides_for_-catenin_binding/26355073 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis Chemical sciences Medicinal and biomolecular chemistry E-cadherin α-Catenin β-Catenin BRET Cell–cell adhesion |
| dc.title.none.fl_str_mv | Engineering β-catenin-derived peptides for α-catenin binding |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <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> |
| eu_rights_str_mv | openAccess |
| id | Manara2_eceec2cf11d0e2685eb88c4e843c3733 |
| identifier_str_mv | 10.1007/s42247-024-00663-8 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26355073 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Engineering β-catenin-derived peptides for α-catenin bindingS. M. Nasir Uddin (19198030)Saad Rasool (9764093)Anupriya M. Geethakumari (17052375)Wesam S. Ahmed (10170053)Kabir H. Biswas (5705864)Biomedical and clinical sciencesMedical biochemistry and metabolomicsOncology and carcinogenesisChemical sciencesMedicinal and biomolecular chemistryE-cadherinα-Cateninβ-CateninBRETCell–cell adhesion<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>2024-03-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s42247-024-00663-8https://figshare.com/articles/journal_contribution/Engineering_-catenin-derived_peptides_for_-catenin_binding/26355073CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/263550732024-03-06T03:00:00Z |
| spellingShingle | Engineering β-catenin-derived peptides for α-catenin binding S. M. Nasir Uddin (19198030) Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis Chemical sciences Medicinal and biomolecular chemistry E-cadherin α-Catenin β-Catenin BRET Cell–cell adhesion |
| status_str | publishedVersion |
| title | Engineering β-catenin-derived peptides for α-catenin binding |
| title_full | Engineering β-catenin-derived peptides for α-catenin binding |
| title_fullStr | Engineering β-catenin-derived peptides for α-catenin binding |
| title_full_unstemmed | Engineering β-catenin-derived peptides for α-catenin binding |
| title_short | Engineering β-catenin-derived peptides for α-catenin binding |
| title_sort | Engineering β-catenin-derived peptides for α-catenin binding |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis Chemical sciences Medicinal and biomolecular chemistry E-cadherin α-Catenin β-Catenin BRET Cell–cell adhesion |