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
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Wiley |
| Uncontrolled Keywords: | Atypical cadherins; Cadherin-23; Cell-cell adhesion; Molecular Dynamics; Single-molecule force spectroscopy (SMFS); Small-angle X-ray scattering (SAXS); single-molecule Fluorescence resonance energy transfer (smFRET) |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 06 Dec 2019 15:24 |
| Last Modified: | 06 Dec 2019 15:24 |
| URI: | http://crdd.osdd.net/open/id/eprint/2509 |
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