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@ARTICLE{Tucholski:1052081,
      author       = {Tucholski, Florian T. and Sternke-Hoffmann, Rebecca and
                      Pauly, Thomas and Norrild, Rasmus K. and Boquoi, Amelie and
                      Fenk, Roland and Nagel, Luitgard and Buell, Alexander K. and
                      Haas, Rainer and Willbold, Dieter},
      title        = {{T}racking reduction-induced molecular changes in
                      pathological free light chains by {SV}-{AUC}},
      journal      = {European biophysics journal},
      volume       = {54},
      number       = {6},
      issn         = {0340-1057},
      address      = {New York},
      publisher    = {Springer},
      reportid     = {FZJ-2026-00749},
      pages        = {365 - 383},
      year         = {2025},
      abstract     = {Multiple myeloma is a blood cancer characterized by plasma
                      cell proliferation and excessive production of monoclonal
                      proteins, often leading to renal complications and other
                      forms of organ damage. A set of nine immunoglobulin free
                      light chain (FLC) samples purified from urine of multiple
                      myeloma patients was subjected to sedimentation velocity
                      analysis. Aim of the study was to track changes of the
                      oligomerization state of each FLC while triggering
                      reduction-induced aggregation into larger structures.
                      Sedimentation velocity experiments, combined with further
                      techniques sensitive to structural changes, were performed
                      to determine the degree of FLC oligomerization in each
                      patient sample under different experimental conditions.
                      Structurally, the FLC monomers are stabilized by two
                      intramolecular disulfide bonds, while covalent dimerization
                      occurs through an unpaired C-terminal cysteine residue.
                      Incubation with the reducing agent TCEP cleaves intra- and
                      intermolecular disulfide bonds, destabilizing both monomers
                      and dimers. Remarkably, different incubation times revealed
                      that destabilized dimers do not dissociate into stable
                      monomers but instead accumulate directly into oligomers and
                      higher-order aggregates. In addition to larger aggregates,
                      fragments with sizes around 1 S were detected with
                      increasing TCEP incubation time. This fragmentation behavior
                      was consistent among FLCs originating from the
                      immunoglobulin kappa variable 1-33 gene (IGKV1-33).
                      Sedimentation velocity-based characterization of FLCs can
                      provide insights into the relationship between their
                      stability and aggregation capacity. An understanding of this
                      relationship is crucial for the development of therapeutic
                      strategies to prevent renal complications associated with
                      monoclonal gammopathies such as multiple myeloma.},
      cin          = {IBI-7},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5244},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1007/s00249-025-01788-2},
      url          = {https://juser.fz-juelich.de/record/1052081},
}