Title
Characterization of <tex>$\beta2$</tex>-microglobulin conformational intermediates associated to different fibrillation conditions Characterization of <tex>$\beta2$</tex>-microglobulin conformational intermediates associated to different fibrillation conditions
Author
Faculty/Department
Faculty of Sciences. Chemistry
Publication type
article
Publication
Chichester ,
Subject
Chemistry
Source (journal)
Journal of mass spectrometry. - Chichester
Volume/pages
46(2011) :8 , p. 734-741
ISSN
1076-5174
ISI
000294521800002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/b99276/5bee8b549d9.pdf
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