In Vitro Aggregation Behavior of a Non-Amyloidogenic λ Light Chain Dimer Deriving from U266 Multiple Myeloma Cells
| LEADER | caa a22 4500 | ||
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| 001 | 528787195 | ||
| 005 | 20181214030152.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924e20120314xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000048393 |2 doi |
| 024 | 7 | 0 | |a 10.1371/journal.pone.0033372 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/48393 | ||
| 245 | 0 | 0 | |a In Vitro Aggregation Behavior of a Non-Amyloidogenic λ Light Chain Dimer Deriving from U266 Multiple Myeloma Cells |h [Elektronische Daten] |c [Paolo Arosio, Marta Owczarz, Thomas Müller-Späth, Paola Rognoni, Marten Beeg, Hua; id_orcid 0000-0002-2805-4612 Wu, Mario Salmona, Massimo Morbidelli] |
| 246 | 0 | |a PLoS ONE | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL) and light chain deposition diseases (LCDD). In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature Tm at pH 7.4). The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO4−≫Cl−>H2PO4−, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding. | |
| 540 | |a Creative Commons Attribution 3.0 Unported |u http://creativecommons.org/licenses/by/3.0 |2 ethresearch | ||
| 700 | 1 | |a Arosio |D Paolo |e joint author | |
| 700 | 1 | |a Owczarz |D Marta |e joint author | |
| 700 | 1 | |a Müller-Späth |D Thomas |e joint author | |
| 700 | 1 | |a Rognoni |D Paola |e joint author | |
| 700 | 1 | |a Beeg |D Marten |e joint author | |
| 700 | 1 | |a Wu |D Hua; id_orcid 0000-0002-2805-4612 |e joint author | |
| 700 | 1 | |a Salmona |D Mario |e joint author | |
| 700 | 1 | |a Morbidelli |D Massimo |e joint author | |
| 773 | 0 | |t PLoS ONE |d Public Library of Science |g 7 (3), p. e33372 |x 1932-6203 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/48393 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/48393 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Arosio |D Paolo |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Owczarz |D Marta |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Müller-Späth |D Thomas |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Rognoni |D Paola |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Beeg |D Marten |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Wu |D Hua; id_orcid 0000-0002-2805-4612 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Salmona |D Mario |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Morbidelli |D Massimo |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t PLoS ONE |d Public Library of Science |g 7 (3), p. e33372 |x 1932-6203 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||