Exploring the 'aggregation-prone' core of human Cystatin C: A structural study.

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Μονάδα:
Τμήμα Βιολογίας
Τίτλος:
Exploring the 'aggregation-prone' core of human Cystatin C: A structural study.
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Έτος δημοσίευσης:
2015
Συγγραφείς:
Paraskevi Tsiolaki
Nikolaos Louros
Stavros Hamodrakas
Vassiliki Iconomidou
Περιοδικό:
Journal of structural biology
Εκδότης:
Elsevier
Τόμος:
191
Αριθμός / τεύχος:
3
Σελίδες:
272-280
Λέξεις-κλειδιά:
Human Cystatin C, Hereditary Cystatin C Amyloid Angiopathy, Stefin 3D-domain swapping, ‘Aggregation-prone’ peptides, Amyloid fibrils
Κύρια θεματική κατηγορία:
Θετικές Επιστήμες
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