Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells
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 cli...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
Portland Press Ltd.
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/13910 |
| _version_ | 1848748475344224256 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hutchinson, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:05:38Z |
| format | Journal Article |
| id | curtin-20.500.11937-13910 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:05:38Z |
| publishDate | 2013 |
| publisher | Portland Press Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-139102017-09-13T15:01:03Z Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells 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 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. 2013 Journal Article http://hdl.handle.net/20.500.11937/13910 10.1042/BJ20130575 Portland Press Ltd. unknown |
| spellingShingle | 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 Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| title | Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| title_full | Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| title_fullStr | Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| title_full_unstemmed | Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| title_short | Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| title_sort | formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cells |
| url | http://hdl.handle.net/20.500.11937/13910 |