@article{open2509,
           month = {November},
           title = {Structural basis of the strong cell-cell junction formed by cadherin-23.},
          author = {G S Singaraju and A Sagar and A Kumar and J S Samuel and J P Hazra and M K Sannigrahi and R M Yennamalli and Fnu Ashish and S Rakshit},
       publisher = {Wiley},
            year = {2019},
            note = {Copyright of this article belongs to Wiley},
         journal = {The FEBS journal},
        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)},
             url = {http://crdd.osdd.net/open/2509/},
        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 {\texttt{\char126}}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.}
}