Micro-heterogeneity and Aggregation in Beta2-microglobulin Solutions: Effects of Temperature, PH, and Conformational Variant Addition
Overview
Authors
Affiliations
We show that beta(2)-microglobulin solutions in physiological conditions contain a tiny fraction of aggregates, which can hardly be filtered out and tend to re-form spontaneously. At physiological pH the fractional amount and size distribution of the latter aggregates do not depend on temperature. Conversely, in the pH range typical of the peri-articular tissue acidosis that often occurs in hemodialysis, temperature increase leads to fast and irreversible growth of the aggregates. Quite similar, but strongly enhanced aggregation effects can be induced even in physiological conditions by adding a very small amount of DeltaN6, a naturally occurring truncated isoform of beta(2)-m known to promote fibrillogenesis.
The Early Phase of β2-Microglobulin Aggregation: Perspectives From Molecular Simulations.
Loureiro R, Faisca P Front Mol Biosci. 2020; 7:578433.
PMID: 33134317 PMC: 7550760. DOI: 10.3389/fmolb.2020.578433.
Loureiro R, Vila-Vicosa D, Machuqueiro M, Shakhnovich E, Faisca P Biomolecules. 2019; 9(8).
PMID: 31416179 PMC: 6722664. DOI: 10.3390/biom9080366.
Co-fibrillogenesis of Wild-type and D76N β2-Microglobulin: THE CRUCIAL ROLE OF FIBRILLAR SEEDS.
Natalello A, Mangione P, Giorgetti S, Porcari R, Marchese L, Zorzoli I J Biol Chem. 2016; 291(18):9678-89.
PMID: 26921323 PMC: 4850305. DOI: 10.1074/jbc.M116.720573.
Systemic amyloidosis: lessons from β2-microglobulin.
Stoppini M, Bellotti V J Biol Chem. 2015; 290(16):9951-8.
PMID: 25750126 PMC: 4400370. DOI: 10.1074/jbc.R115.639799.
Misfolding of amyloidogenic proteins and their interactions with membranes.
Relini A, Marano N, Gliozzi A Biomolecules. 2014; 4(1):20-55.
PMID: 24970204 PMC: 4030986. DOI: 10.3390/biom4010020.