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

Santambrogio, C., Ricagno, S., Sobott, F., Colombo, M., Bolognesi, M., Grandori, R. (2011). Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions. JOURNAL OF MASS SPECTROMETRY, 46, 734-741 [10.1002/jms.1946].

Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions

SANTAMBROGIO, CARLO;GRANDORI, RITA
2011

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 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
Articolo in rivista - Articolo scientifico
Amyloidogenic intermediate; dialysis-related amyloidosis; electrospray ionisation–mass spectrometry; ion mobility spectrometry; circular dichroism
English
2011
46
734
741
none
Santambrogio, C., Ricagno, S., Sobott, F., Colombo, M., Bolognesi, M., Grandori, R. (2011). Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions. JOURNAL OF MASS SPECTROMETRY, 46, 734-741 [10.1002/jms.1946].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/36703
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