Curtin University Homepage
  • Library
  • FAQ
    • Log in

    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

    Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells

    Access Status
    Open access via publisher
    Authors
    Hutchinson, A.
    Malik, A.
    Berkahn, M.
    Agostino, Mark
    To, J.
    Tacchi, J.
    Djordjevic, S.
    Turnbull, L.
    Whitchurch, C.
    Edmundson, A.
    Jones, D.
    Raison, R.
    Ramsland, Paul
    Date
    2013
    Collection
    • Curtin Research Publications
    Type
    Journal Article
    Metadata
    Show full item record
    Abstract

    We have described the presence of cell-membrane-associated ?FLCs (free immunoglobulin light chains) on the surface of myeloma cells. Notably, the anti-?FLC mAb (monoclonal antibody) MDX-1097 is being assessed in clinical trials as a therapy for ? light chain isotype multiple myeloma. Despite the clinical potential of anti-FLC mAbs, there have been limited studies on characterizing membrane-associated FLCs at a molecular level. Furthermore, it is not known whether ?FLCs can associate with cell membranes of myeloma cells. In the present paper, we describe the presence of ?FLCs on the surface of myeloma cells. We found that cell-surface-associated ?FLCs are bound directly to the membrane and in an aggregated form. Subsequently, membrane interaction studies revealed that ?FLCs interact with saturated zwitterionic lipids such as phosphatidylcholine and phosphatidylethanolamine, and using automated docking, we characterize a potential recognition site for these lipids. Atomic force microscopy confirmed that membrane-associated ?FLCs are aggregated. Given the present findings, we propose a model whereby individual FLCs show modest affinity for zwitterionic lipids, with aggregation stabilizing the interaction due to multivalency. Notably, this is the first study to image FLCs bound to phospholipids and provides important insights into the possible mechanisms of membrane association by this unique myeloma surface antigen.

    Citation
    Hutchinson, A. and Malik, A. and Berkahn, M. and Agostino, M. and To, J. and Tacchi, J. and Djordjevic, S. et al. 2013. Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells. Biochemical Journal. 454: pp. 479-489.
    Source Title
    Biochemical Journal
    URI
    http://hdl.handle.net/20.500.11937/13910
    DOI
    10.1042/BJ20130575
    Department
    School of Biomedical Sciences

    Related items

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

    • Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
      Hutchinson, A.; Ramsland, Paul; Jones, D.; Agostino, Mark; Lund, M.; Jennings, C.; Bockhorni, V.; Yuriev, E.; Edmundson, A.; Raison, R. (2010)
      Free ? L chains (F?LCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which F?LCs ...
    • Characterization of a unique conformational epitope on free immunoglobulin kappa light chains that is recognized by an antibody with therapeutic potential
      Hutchinson, A.; Alexova, R.; Bockhorni, V.; Ramsland, Paul; Jones, D.; Jennings, C.; Broady, K.; Edmundson, A.; Raison, R. (2011)
      The murine mAb, K-1-21, recognizes a conformational epitope expressed on free Ig kappa light chains (FκLCs) and also on cell membrane-associated FκLCs found on kappa myeloma cells. This has led to the development of a ...
    • The development of a rigorous nanocharacterization scheme for electrochemical systems
      Veder, Jean-Pierre M. (2010)
      This thesis reports on a methodology for the nanocharacterization of complex electrochemical systems. A series of powerful techniques have been adapted and applied to studies of two scientifically important electrochemical ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorsTitlesSubjectsDocument TypesThis CollectionIssue DateAuthorsTitlesSubjectsDocument Types

    My Account

    Log in

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Connect with Curtin

    • 
    • 
    • 
    • 
    • 
    • 
    • 

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

    Send FeedbackContact Us
    DSpace software copyright © 2002-2015  DuraSpace