A potential new, stable state of the E-cadherin strand-swapped dimer in solution
E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a mon...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Published: |
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/54511 |
| _version_ | 1848759389956079616 |
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| author | Schumann-Gillett, A. Mark, A. Deplazes, Evelyne O'Mara, M. |
| author_facet | Schumann-Gillett, A. Mark, A. Deplazes, Evelyne O'Mara, M. |
| author_sort | Schumann-Gillett, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution. |
| first_indexed | 2025-11-14T09:59:07Z |
| format | Journal Article |
| id | curtin-20.500.11937-54511 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:59:07Z |
| publishDate | 2017 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-545112018-06-13T07:33:22Z A potential new, stable state of the E-cadherin strand-swapped dimer in solution Schumann-Gillett, A. Mark, A. Deplazes, Evelyne O'Mara, M. E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution. 2017 Journal Article http://hdl.handle.net/20.500.11937/54511 10.1007/s00249-017-1229-3 fulltext |
| spellingShingle | Schumann-Gillett, A. Mark, A. Deplazes, Evelyne O'Mara, M. A potential new, stable state of the E-cadherin strand-swapped dimer in solution |
| title | A potential new, stable state of the E-cadherin strand-swapped dimer in solution |
| title_full | A potential new, stable state of the E-cadherin strand-swapped dimer in solution |
| title_fullStr | A potential new, stable state of the E-cadherin strand-swapped dimer in solution |
| title_full_unstemmed | A potential new, stable state of the E-cadherin strand-swapped dimer in solution |
| title_short | A potential new, stable state of the E-cadherin strand-swapped dimer in solution |
| title_sort | potential new, stable state of the e-cadherin strand-swapped dimer in solution |
| url | http://hdl.handle.net/20.500.11937/54511 |