Micro-heterogeneity and aggregation in beta2-microglobulin solutions: effects of temperature, pH, and conformational variant addition.
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.
Piazza
Roberto
R
Dipartimento di Ingegneria Nucleare, Politecnico di Milano, via Ponzio 34/3, 20133, Milano, Italy. roberto.piazza@polimi.it
Pierno
Matteo
M
Iacopini
Sara
S
Mangione
Palma
P
Esposito
Gennaro
G
Bellotti
Vittorio
V
D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D008832:Microchemistry / Q000379:methods; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011487:Protein Conformation; D012996:Solutions; D013696:Temperature; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000648:ultrastructure*
D046912:Multiprotein Complexes; D012996:Solutions; D001613:beta 2-Microglobulin