Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/3359
Title: Structural basis of the strong cell‐cell junction formed by cadherin‐23
Authors: Singaraju, G.S.
Sagar, A.
Kumar, Anuj
Samuel, J.S.
Hazra, J.P.
Sannigrahi, M.K.
Rakshit, S.
Keywords: Atypical cadherins
Cadherin‐23
Cell–cell adhesion
Single-molecule Forster resonance energy transfer small‐angle X‐ray scattering
Small‐angle X‐ray scattering
Issue Date: 2020
Publisher: Blackwell Publishing
Citation: FEBS Journal, 287(11), pp.2328-2347.
Abstract: Cadherin‐23, a giant atypical cadherin, form 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 ~ 8 × 10−4 s−1 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.
Description: Only IISERM authors are available in the record.
URI: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15141
http://hdl.handle.net/123456789/3359
Appears in Collections:Research Articles

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