Title
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Characterization of -microglobulin conformational intermediates associated to different fibrillation conditions
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Author
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Abstract
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β2-Microglobulin (β2m) is the light chain of the class-I major histocompatibility complex, being also the causing agent of dialysis-related amyloidosis, which results from its accumulation as amyloid material in the skeletal joints. This study describes conformational properties of β2m under two distinct, in vitro amyloidogenic conditions: neutral pH in the presence of 20% 2,2,2-trifluoroethanol (TFE) and acidic pH in the absence of TFE. Species distribution analysis by electrospray ionizationmass spectrometry (ESI-MS) is combined with information obtained by ion mobilitymass spectrometry (IM-MS), fluorescence and circular dichroism (CD) spectroscopy. It is shown that β2m populates quite different conformational ensembles under the two conditions, but both ensembles display a minor fraction of the population in a partially folded state. In spite of similar compactness, these two partially folded forms display different conformations: helical secondary structure is predominant in the species at pH 7.4, 20% TFE, while the low-pH form is mainly random coil. As temperature is increased, the TFE intermediate looses helical structure becoming more similar to the low-pH intermediate. The existence of different conformational ensembles may rationalize the different aggregation propensity displayed by β2m under the two fibrillation conditions analyzed here. |
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Language
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English
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Source (journal)
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Journal of mass spectrometry. - Chichester
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Publication
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Chichester
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2011
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ISSN
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1076-5174
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DOI
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10.1002/JMS.1946
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Volume/pages
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46
:8
(2011)
, p. 734-741
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ISI
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000294521800002
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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