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dc.contributor.author
Arosio, Paolo
dc.contributor.author
Owczarz, Marta
dc.contributor.author
Müller-Späth, Thomas
dc.contributor.author
Rognoni, Paola
dc.contributor.author
Beeg, Marten
dc.contributor.author
Wu, Hua
dc.contributor.author
Salmona, Mario
dc.contributor.author
Morbidelli, Massimo
dc.date.accessioned
2018-09-20T12:33:24Z
dc.date.available
2017-06-09T23:31:44Z
dc.date.available
2018-09-20T12:33:24Z
dc.date.issued
2012-03-14
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0033372
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/48393
dc.identifier.doi
10.3929/ethz-b-000048393
dc.description.abstract
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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
In Vitro Aggregation Behavior of a Non-Amyloidogenic λ Light Chain Dimer Deriving from U266 Multiple Myeloma Cells
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
7
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e33372
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02516 - Inst. f. Chemie- und Bioingenieurwiss. / Inst. Chemical and Bioengineering::03451 - Morbidelli, Massimo (emeritus) / Morbidelli, Massimo (emeritus)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02516 - Inst. f. Chemie- und Bioingenieurwiss. / Inst. Chemical and Bioengineering::03451 - Morbidelli, Massimo (emeritus) / Morbidelli, Massimo (emeritus)
ethz.date.deposited
2017-06-09T23:34:48Z
ethz.source
ECIT
ethz.identifier.importid
imp59364f286c16469756
ethz.ecitpid
pub:79687
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T20:53:47Z
ethz.rosetta.lastUpdated
2021-02-15T01:50:04Z
ethz.rosetta.versionExported
true
ethz.COinS
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