Publication
Title
Characterization of -microglobulin conformational intermediates associated to different fibrillation conditions
Author
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.
Language
English
Source (journal)
Journal of mass spectrometry. - Chichester
Journal of mass spectrometry. - Chichester
Publication
Chichester : 2011
ISSN
1076-5174
Volume/pages
46 :8 (2011) , p. 734-741
ISI
000294521800002
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Determination of subunit composition and architecture of supramolecular and biological complexes using mass spectrometry coupled with ion mobility spectroscopy and allied techniques.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 28.11.2011
Last edited 20.09.2021
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