title: Structural basis of the strong cell-cell junction formed by cadherin-23.
creator: Singaraju, G S
creator: Sagar, A
creator: Kumar, A
creator: Samuel, J S
creator: Hazra, J P
creator: Sannigrahi, M K
creator: Yennamalli, R M
creator: Ashish, Fnu
creator: Rakshit, S
subject: QR Microbiology
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.
publisher: Wiley
date: 2019-11-15
type: Article
type: PeerReviewed
relation: https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.15141
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     
relation: http://crdd.osdd.net/open/2509/