Amyloidogenic proteins like human
Cystatin C (hCC) have been shown to form dimers and oligomers by exchange of subdomains of the monomeric
proteins. Normally, the hCC monomer, a low molecular type 2
Cystatin, consists of 120
amino acid residues and functions as an inhibitor of
cysteine proteases. The oligomerization of hCC is involved in the pathophysiology of a rare form of
amyloidosis namely Icelandic
hereditary cerebral amyloid angiopathy, in which an L68Q mutant is deposited as
amyloid in brain arteries of young adults. In order to find the shortest stretch responsible to drive the fibril formation of hCC, we have previously demonstrated that the LQVVR
peptide forms
amyloid fibrils, in vitro (Tsiolaki et al., 2015). Predictions by AMYLPRED, an amyloidogenic determinant prediction algorithm developed in our lab, led us to synthesize and experimentally study two additional predicted
peptides derived from hCC. Along with our previous findings, in this work, we reveal that these
peptides self-assemble, in a similar way, into
amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and
Congo red staining studies have shown. Further to our experimental results, all three
peptides seem to have a fundamental contribution in forming the "aggregation-prone" core of human
Cystatin C.