A potential new, stable state of the E-cadherin strand-swapped dimer in solution

Schumann-Gillett, Alexandra, Mark, Alan E., Deplazes, Evelyne and O'Mara, Megan L. (2017) A potential new, stable state of the E-cadherin strand-swapped dimer in solution. European Biophysics Journal, . doi:10.1007/s00249-017-1229-3

Author Schumann-Gillett, Alexandra
Mark, Alan E.
Deplazes, Evelyne
O'Mara, Megan L.
Title A potential new, stable state of the E-cadherin strand-swapped dimer in solution
Journal name European Biophysics Journal   Check publisher's open access policy
ISSN 1432-1017
Publication date 2017-06-15
Sub-type Article (original research)
DOI 10.1007/s00249-017-1229-3
Open Access Status Not yet assessed
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
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.
Keyword Converged structure
Molecular dynamics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
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Created: Tue, 04 Jul 2017, 13:22:03 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences