Crystal structure and immunological properties of the first annexin from Schistosoma mansoni: insights into the structural integrity of the schistosomal tegument

Authors

  • Chiuan Yee Leow,

    1. School of Veterinary Science, University of Queensland, Gatton, Australia
    2. Queensland Institute of Medical Research, Herston, Australia
    3. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia
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    • These authors made equal contributions to the work
  • Charlene Willis,

    1. Queensland Institute of Medical Research, Herston, Australia
    2. Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Australia
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    • These authors made equal contributions to the work
  • Asiah Osman,

    1. Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Australia
    Current affiliation:
    1. Drug Discovery Centre, Forest Research Institute Malaysia, Kepong, Malaysia
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    • These authors made equal contributions to the work
  • Lyndel Mason,

    1. Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Australia
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  • Anne Simon,

    1. Université Lyon 1, Villeurbanne, and Laboratoire Chimie et Biologie des Membranes et des Nanoobjets, Université Bordeaux, Pessac, France
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  • Brian J. Smith,

    1. La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
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  • Robin B. Gasser,

    1. Faculty of Veterinary Science, University of Melbourne, Parkville, Australia
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  • Malcolm K. Jones,

    Corresponding author
    1. School of Veterinary Science, University of Queensland, Gatton, Australia
    2. Queensland Institute of Medical Research, Herston, Australia
    • Correspondence

      A. Hofmann, Structural Chemistry Program, Eskitis Institute, Griffith University, N75 Don Young Road, Nathan, Qld 4111, Australia

      Fax: +61-7-3735-4425

      Tel: +61-7-3735-4425

      E-mail: a.hofmann@griffith.edu.au

      M. K. Jones, School of Veterinary Sciences, University of Queensland, Gatton, Qld 4343, Australia

      Fax: +61-7-3362-0106

      Tel: +61-7-3362-0197

      E-mail: m.jones@uq.edu.au

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  • Andreas Hofmann

    Corresponding author
    1. Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Australia
    2. Faculty of Veterinary Science, University of Melbourne, Parkville, Australia
    3. Queensland Tropical Health Alliance, Smithfield, Australia
    • Correspondence

      A. Hofmann, Structural Chemistry Program, Eskitis Institute, Griffith University, N75 Don Young Road, Nathan, Qld 4111, Australia

      Fax: +61-7-3735-4425

      Tel: +61-7-3735-4425

      E-mail: a.hofmann@griffith.edu.au

      M. K. Jones, School of Veterinary Sciences, University of Queensland, Gatton, Qld 4343, Australia

      Fax: +61-7-3362-0106

      Tel: +61-7-3362-0197

      E-mail: m.jones@uq.edu.au

    Search for more papers by this author

Abstract

Schistosomiasis is a major parasitic disease of humans, second only to malaria in its global impact. The disease is caused by digenean trematodes that infest the vasculature of their human hosts. These flukes are limited externally by a body wall composed of a syncytial epithelium, the apical surface membrane of which is a parasitism-adapted dual membrane complex. Annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the first structural and immunobiochemical characterization of an annexin from Schistosoma mansoni. The crystal structure of annexin B22 confirms the presence of the previously predicted α-helical segment in the II/III linker and reveals a covalently linked head-to-head dimer. From the calcium-bound crystal structure of this protein, canonical type II, type III and B site positions are occupied, and a novel binding site has been identified. The dimer arrangement observed in the crystal structure suggests the presence of two prominent features, a potential non-canonical membrane binding site and a potential binding groove opposite to the former. Results from transcriptional profiling during development show that annexin B22 expression is correlated with life stages of the parasite that possess the syncytial tegument layer, and ultrastructural localization by immuno-electron microscopy confirms the occurrence of annexins in the tegument of S. mansoni. Data from membrane binding and aggregation assays indicate the presence of differential molecular mechanisms and support the hypothesis of annexin B22 providing structural integrity in the tegument.

Database

Coordinates and structure factors have been deposited with the PDB, accession numbers 4mdu, 4mdv

Structured digital abstract

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