title: Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions.
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.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20133-Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Santambrogio
authors.forename: Stefano
authors.initials: S
authors.lastname: Ricagno
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.forename: Matteo
authors.initials: M
authors.lastname: Colombo
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D017510:Protein Folding; D006435:Renal Dialysis; D021241:Spectrometry, Mass, Electrospray Ionization; D014270:Trifluoroethanol; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000682:Amyloid; D001613:beta 2-Microglobulin; D014270:Trifluoroethanol