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 ionization-mass spectrometry (ESI-MS) is combined with information obtained by ion mobility-mass 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.
Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions / C. Santambrogio, S. Ricagno, F. Sobott, M. Colombo, M. Bolognesi, R. Grandori. - In: JOURNAL OF MASS SPECTROMETRY. - ISSN 1076-5174. - 46:8(2011), pp. 734-741.
|Titolo:||Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions|
RICAGNO, STEFANO (Secondo)
BOLOGNESI, MARTINO (Penultimo)
|Parole Chiave:||amyloidogenic intermediate ; dialysis-related amyloidosis ; electrospray ionisation–mass spectrometry ; ion mobility spectrometry ; circular dichroism|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/jms.1946|
|Appare nelle tipologie:||01 - Articolo su periodico|