Amyloidogenic properties of the artificial protein albebetin and its biologically active derivatives. The role of electrostatic interactions in fibril formation.
The artificial protein albebetin (ABB) and its derivatives containing biologically active fragments of natural proteins form fibrils at physiological pH. The amyloid nature of the fibrils was confirmed by far UV circular dichroism spectra indicating for rich beta-structure, thioflavin T binding assays, and examination of the obtained polymers by atomic force microscopy. Fusing of short peptides--octapeptide of human alpha(2)-interferon (130-137) or hexapeptide HLDF-6 (41-46) of human leukemia differentiation factor--with the N-terminus of ABB led to increased amyloidogenicity of the protein: the rate of fibril formation increased and the morphology of fibrils became more complex. The presence of free hexapeptide HLDF-6 in the ABB solution had the same effect. Increasing ionic strength also activated the process of amyloid formation, but to less extent than did the peptides fused with ABB or added to the ABB solution. We suggest an important role of electrostatic interactions in formation of ABB fibrils. The foregoing ways (addition of salt or peptides) allow decrease in electrostatic repulsion between ABB molecules carrying large negative charge (-12) at neutral pH, thus promoting fibril formation.
Lavrikova
M A
MA
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow. marikalav@vega.protres.ru
Zamotin
V V
VV
Malisauskas
M
M
Chertkova
R V
RV
Kostanyan
I A
IA
Dolgikh
D A
DA
Kirpichnikov
M P
MP
Morozova-Roche
L A
LA
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity
D000682:Amyloid; D009363:Neoplasm Proteins; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; C091149:cell differentiation factor 8.2-kDa; C074146:albebetin