VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • Introduction of glutamines into the B2-H2 loop promotes prion protein conversion
    Avbelj, Matevž, 1982- ; Hafner Bratkovič, Iva, 1978- ; Jerala, Roman
    In prion diseases cellular prion protein (PrPC) undergoes conformational transition into the ß-sheet-rich form (PrPSc). PrPC consists of the disordered N-terminal part and a C-terminal globular ... domain containing three alpha helices (H1, H2, H3) and an antiparallel beta sheet (B1, B2). B2-H2 loop, which has a focal role in the species barrier, contains the highest density of asparagine (N) and glutamine (Q) residues in the whole sequence. Q/N-rich domains are essential for the conversion of yeast prions. We investigated the role of Q/N residues in the B2-H2 loop in PrP conversion. We prepared mouse PrP mutants with increasing number of consecutive Q/N residues in the B2-H2 loop. Stability of the mutants decreased with the increasing number of inserted glutamines. In vitro conversion of mutants yielded fibrils of similar morphology as the wild-type PrP. Q/N mutants accelerated fibrillization in comparison to the wild-type PrP, with mutant containing the most glutamines having the shortest lag phase. The effect of Q/N residues was specific for the B2-H2 loop and was not due to simple increase in flexibility as the introduction of Gly-Ser or Ala residues slowed the conversion despite their decreased stability. Our results thus suggest that Q/N residues in the B2-H2 loop of PrP promote protein conversion and may represent a link to conversion of Q/N-rich prions.
    Vir: Biochemical and biophysical research communications. - ISSN 0006-291X (Vol. 413, issue 3, 2011, str. 521-526)
    Vrsta gradiva - članek, sestavni del
    Leto - 2011
    Jezik - angleški
    COBISS.SI-ID - 4766234
    DOI

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