It is assumed that protein fibrils manifested in amyloidosis result from an
aggregation reaction involving small misfolded protein sequences being
in an ‘oligomeric’ or ‘prefibrillar’ state. This review covers recent optical
spectroscopic studies of amyloid protein misfolding, oligomerization and
amyloid fibril growth.
Cleavage of the small amyloidogenic proteinb2-microglobulin after lysine-58 renders it more prone to unfolding and aggregation. This is important
for dialysis-related b2
-microglobulin amyloidosis, since elevated levels of
cleaved b2-microglobulin may be found in the circulation of dialysis
The discovery of prion disease and the establishment of the protein only
hypothesis of prion propagation raised substantial interest in the class of
maladies referred to as conformational diseases. Although significant pro-gress has been made in elucidating the mechanisms of polymerization for
several amyloidogenic proteins and peptides linked to conformational dis-
a-lactalbumin (LA) in its molten globule (MG) state at low pH forms
amyloid fibrils. Here, we have studied the aggregation propensities of LA
derivatives characterized by a single peptide bond fission (1–40⁄41–123,
named Th1-LA) or a deletion of a chain segment of 12 amino acid resi-dues located at the level of the b-subdomain of the native protein (1–
40⁄53–123, named desb-LA). We have also compared the early stages of
the aggregation process of these LA derivatives with those of intact LA....
In spiders soluble proteins are converted to form insoluble
silk fibres, stronger than steel. The final fibre product has
longbeen the subject of study;however, little is knownabout
the conversion process in the silk-producing gland of the
spider. Here we describe a study of the conversion of the
soluble form of the major spider-silk protein, spidroin,
directly extracted from the silk gland, to ab-sheet enriched
stateusing circular dichroism(CD) spectroscopy.
Although ADAM10 is a majora-secretase involved in non-amyloidogenic
processing of the amyloid precursor protein, several additional substrates
have been identified, most of them in vitro. Thus, therapeutical
approaches for the prevention of Alzheimer’s disease by upregulation of
this metalloproteinase may have severe side effects.
Amyloid deposits with Arg124 mutated TGFBI protein
havebeen identified inautosomal dominant blindingcorneal
dystrophies.We assessedin vitrothe mechanisms determin-ing TGFBI protein amyloid transformation involving
mutations of Arg124.Eight peptides synthesized following
the TGFBI protein sequence, centered on codon Arg124
holding the previously reported amyloidogenic mutations
and the respective controls were studied.Cys124 andHis124
mutated peptide preparations contained significantly higher
amounts of amyloid than the native peptide....