@article{FabianGastLaueetal.2008,
  author    = {Fabian, Heinz and Gast, Klaus and Laue, Michael and Misselwitz, Rolf and Uchanska-Ziegler, Barbara and Ziegler, Andreas and Naumann, Dieter},
  title     = {Early stages of misfolding and association of beta2-microglobulin : insights from infrared spectroscopy and dynamic light scattering},
  year      = {2008},
  abstract  = {Conformational changes associated with the assembly of recombinant ;2-microglobulin in vitro under acidic conditions were investigated using infrared spectroscopy and static and dynamic light scattering. In parallel, the morphology of the different aggregated species obtained under defined conditions was characterized by electron microscopy. The initial salt-induced aggregate form of ;2-microglobulin, composed of small oligomers (dimers to tetramers), revealed the presence of ;-strands organized in an intramolecular-like fashion. Further particle growth was accompanied by the formation of intermolecular ;-sheet structure and led to short curved forms. An increase in temperature by only 25 °C was able to disaggregate these assemblies, followed by the formation of longer filamentous structures. In contrast, a rise in temperature up to 100 °C was associated with a reorganization of the short curved forms at the level of secondary structure and the state of assembly, leading to a species with a characteristic infrared spectrum different from those of all the other aggregates observed before, suggesting a unique overall structure. The infrared spectral features of this species were nearly identical to those of ;2-microglobulin assemblies formed at low ionic strength with agitation, indicating the presence of fibrils, which was confirmed by electron microscopy. The observed spectroscopic changes suggest that the heat-triggered conversion of the short curved assemblies into fibrils involves a reorganization of the ;-strands from an antiparallel arrangement to a parallel arrangement, with the latter being characteristic of amyloid fibrils of ;2-microglobulin.},
  language  = {en}
}
@article{FabianGastLaueetal.2013,
  author    = {Fabian, Heinz and Gast, Klaus and Laue, Michael and Jetzschmann, Katharina J. and Naumann, Dieter and Ziegler, Andreas and Uchanska-Ziegler, Barbara},
  title     = {IR spectroscopic analyses of amyloid fibril formation of beta(2)-microglobulin using a simplified procedure for its in vitro generation at neutral pH},
  series = {Biophysical chemistry : an international journal devoted to the physical chemistry of biological phenomena},
  volume    = {179},
  journal   = {Biophysical chemistry : an international journal devoted to the physical chemistry of biological phenomena},
  number    = {5},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0301-4622},
  doi       = {10.1016/j.bpc.2013.05.001},
  pages     = {35 -- 46},
  year      = {2013},
  abstract  = {beta(2)-microglobulin (beta(2)m) is known to be the major component of fibrillar deposits in the joints of patients suffering from dialysis-related amyloidosis. We have developed a simplified procedure to convert monomeric recombinant beta(2)m into amyloid fibrils at physiological pH by a combination of stirring and heating, enabling us to follow conformational changes associated with the assembly by infrared spectroscopy and electron microscopy. Our studies reveal that fibrillogenesis begins with the formation of relatively large aggregates, with secondary structure not significantly altered by the stirring-induced association. In contrast, the conversion of the amorphous aggregates into amyloid fibrils is associated with a profound re-organization at the level of the secondary and tertiary structures, leading to non-native like parallel arrangements of the beta-strands in the fully formed amyloid structure of beta(2)m. This study highlights the power of an approach to investigate the formation of beta(2)m fibrils by a combination of biophysical techniques including IR spectroscopy.},
  language  = {en}
}