title: Folding and fibrillogenesis: clues from beta2-microglobulin.
abstract: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, I-33100 Udine, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rennella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.forename: Paolo
authors.initials: P
authors.lastname: Viglino
authors.forename: Riccardo
authors.initials: R
authors.lastname: Porcari
authors.forename: Laura
authors.initials: L
authors.lastname: Verga
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
mesh_terms: 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
chemical_list: D000682:Amyloid; D050505:Mutant Proteins; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D014270:Trifluoroethanol