Structural basis of the strong cell-cell junction formed by cadherin-23.
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
Structural basis of the strong cell-cell junction formed by cadherin-23.
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| Creator |
Singaraju, G S
Sagar, A Kumar, A Samuel, J S Hazra, J P Sannigrahi, M K Yennamalli, R M Ashish, Fnu Rakshit, S |
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| Subject |
QR Microbiology
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| Description |
Cadherin-23, a giant atypical cadherin, forms homophilic interactions at the cell-cell junction of epithelial cells and heterophilic interactions with protocadherin-15 at the tip-links of neuroepithelial cells. While the molecular structure of the heterodimer is solved, the homodimer structure is yet to be resolved. The homodimers play an essential role in cell-cell adhesion as the downregulation of cadherin-23 in cancers loosen the intercellular junction resulting in faster-migration of cancer cells and a significant drop in patient survival. In vitro studies have measured a stronger aggregation-propensity of cadherin-23 compared to typical E-cadherin. Here, we deciphered the unique trans-homodimer structure of cadherin-23 in solution, and show that it consists of two electrostatic-based interfaces extended up to two terminal domains. The interface is robust, with a low off-rate of ~8x10 s that supports its strong aggregation-propensity. We identified a point-mutation, E78K, that disrupts this binding. Interestingly, a mutation at the interface was reported in skin cancer. Overall, the structural basis of the strong cadherin-23 adhesion may have far-reaching applications in the fields of mechanobiology and cancer.
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| Publisher |
Wiley
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| Date |
2019-11-15
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| Type |
Article
PeerReviewed |
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| Relation |
https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.15141
http://crdd.osdd.net/open/2509/ |
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| Identifier |
Singaraju, G S and Sagar, A and Kumar, A and Samuel, J S and Hazra, J P and Sannigrahi, M K and Yennamalli, R M and Ashish, Fnu and Rakshit, S (2019) Structural basis of the strong cell-cell junction formed by cadherin-23. The FEBS journal. ISSN 1742-4658
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