Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

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

    253537.pdf (6.962Mb)
    Access Status
    Open access
    Authors
    Schumann-Gillett, A.
    Mark, A.
    Deplazes, Evelyne
    O'Mara, M.
    Date
    2017
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Schumann-Gillett, A. and Mark, A. and Deplazes, E. and O'Mara, M. 2017. A potential new, stable state of the E-cadherin strand-swapped dimer in solution. European Biophysics Journal. 47 (1): pp. 59-67.
    Source Title
    European Biophysics Journal
    DOI
    10.1007/s00249-017-1229-3
    ISSN
    1432-1017
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/54511
    Collection
    • Curtin Research Publications
    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.

    Related items

    Showing items related by title, author, creator and subject.

    • Structural and Functional Characterization of Ubiquitin Variant Inhibitors of USP15
      Teyra, J.; Singer, A.; Schmitges, F.; Jaynes, P.; Kit Leng Lui, S.; Polyak, M.; Fodil, N.; Krieger, J.; Tong, J.; Schwerdtfeger, C.; Brasher, B.; Ceccarelli, DFJ ; Moffat, J.; Sicheri, F.; Moran, M.; Gros, P.; Eichhorn, Pieter ; Lenter, M.; Boehmelt, G.; Sidhu, S. (2019)
      The multi-domain deubiquitinase USP15 regulates diverse eukaryotic processes and has been implicated in numerous diseases. We developed ubiquitin variants (UbVs) that targeted either the catalytic domain or each of three ...
    • Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma
      Huang, B.; Deng, S.; Loo, S.; Datta, A.; Yap, Y.; Yan, B.; Ooi, C.; Dinh, T.; Zhuo, J.; Tochhawng, L.; Gopinadhan, S.; Jegadeesan, T.; Tan, P.; Salto-Tellez, M.; Yong, W.; Soong, R.; Yeoh, K.; Goh, Y.; Lobie, P.; Yang, H.; Kumar, Alan Prem; Maciver, S.; So, J.; Yap, C. (2016)
      In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC ...
    • Molecular modelling of the interactions of complex carbohydrates with proteins
      Gandhi, Neha Sureshchandra (2011)
      Glycosaminoglycans (GAGs) are ubiquitous complex carbohydrate molecules present on the cell surfaces and in extracellular matrices (ECM) of vertebrate and invertebrate tissues. The interactions of sulphated GAGs such as ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.