Folding and fibrillogenesis: clues from beta2-microglobulin.
Renal failure impairs the clearance of beta(2)-microglobulin from the serum, with the result that this protein accumulates in joints under the form of amyloid fibrils. While the molecular mechanism leading to deposition of amyloid in vivo is not totally understood, some organic compounds, such as trifluoroethanol (TFE), are commonly used to promote the elongation of amyloid fibrils in vitro. This article gives some insights into the structural properties and the conformational states of beta(2)-microglobulin in the presence of TFE, using both the wild-type protein and the mutant Trp60Gly. The structure of the native state of the protein is rather insensitive to the presence of the alcohol, but the stability of this state is lowered in comparison to some other conformational states. In particular, a native-like folding intermediate is observed in the presence of moderate concentrations of TFE. Instead, at higher concentrations of the alcohol, the population of a disordered native-unlike state is dominant and correlates with the ability to elongate fibrils.
Rennella
Enrico
E
Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, I-33100 Udine, Italy.
Corazza
Alessandra
A
Giorgetti
Sofia
S
Fogolari
Federico
F
Viglino
Paolo
P
Porcari
Riccardo
R
Verga
Laura
L
Stoppini
Monica
M
Bellotti
Vittorio
V
Esposito
Gennaro
G
D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics; D014270:Trifluoroethanol; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure
D000682:Amyloid; D050505:Mutant Proteins; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D014270:Trifluoroethanol