Renal failure impairs the clearance of β2-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 β2-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.
