Inhibition of prion amplification by expression of dominant inhibitory mutants--a systematic insertion mutagenesis study.
Standard
Inhibition of prion amplification by expression of dominant inhibitory mutants--a systematic insertion mutagenesis study. / Geissen, Markus; Mella, Harriet; Saalmüller, Armin; Eiden, Martin; Proft, Juliane; Pfaff, Eberhard; Schätzl, Hermann M; Groschup, Martin H.
In: J PEDIAT OPHTH STRAB, Vol. 9, No. 1, 1, 2009, p. 40-47.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Inhibition of prion amplification by expression of dominant inhibitory mutants--a systematic insertion mutagenesis study.
AU - Geissen, Markus
AU - Mella, Harriet
AU - Saalmüller, Armin
AU - Eiden, Martin
AU - Proft, Juliane
AU - Pfaff, Eberhard
AU - Schätzl, Hermann M
AU - Groschup, Martin H
PY - 2009
Y1 - 2009
N2 - Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrP(res) formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4-tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The convertibility was affected not only by introducing the insertion in the putatively refolded region (aa100-170), but also in the C-terminus of PrP (up to aa214). Moreover, dominant inhibitory effects on conversion were observed for PrP-mutants at four distinguished regions (aa100-112; aa130-154; aa166-172, aa196-200). Computer based structural analysis revealed that these segments were organized in two structurally clearly separated regions supporting the idea that they could function as protein-protein interaction sites which are necessary during seed formation.
AB - Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrP(res) formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4-tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The convertibility was affected not only by introducing the insertion in the putatively refolded region (aa100-170), but also in the C-terminus of PrP (up to aa214). Moreover, dominant inhibitory effects on conversion were observed for PrP-mutants at four distinguished regions (aa100-112; aa130-154; aa166-172, aa196-200). Computer based structural analysis revealed that these segments were organized in two structurally clearly separated regions supporting the idea that they could function as protein-protein interaction sites which are necessary during seed formation.
M3 - SCORING: Zeitschriftenaufsatz
VL - 9
SP - 40
EP - 47
JO - J PEDIAT OPHTH STRAB
JF - J PEDIAT OPHTH STRAB
SN - 0191-3913
IS - 1
M1 - 1
ER -
