Abstract
The human prion gene, PRNP, has two allelic forms that encode either a methionine or valine at codon 129. This polymorphism strongly influences the pathogenesis of prion disease. However, the underlying mechanism remains unclear. We compared the conformation between wild-type human prion protein (rPrPC) with either a valine or methionine at position 129, using a panel of monoclonal antibodies that are specific for epitopes along the entire protein. We found that rPrPC(129M) has a more exposed helix 1 region compared to rPrPC(129V). Helix 1 is important in the aggregation process. Accordingly, rPrPC(129M) aggregates at a faster rate and forms more aggregate than rPrPC(129V). In addition, by using a rPrP with a pathogenic mutation of five additional octapeptide repeat insertions, rPrP(129M)/10OR, as "seeds", we showed that rPrP(129M)/10OR promotes the aggregation of rPrPC(129M) more efficiently than rPrPC(129V). These findings provide a possible mechanism underlying the influence of residue 129 on human prion disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 875-881 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 368 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 18 2008 |
| Externally published | Yes |
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Keywords
- Aggregation
- Epitope
- Polymorphism
- Prion protein
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Normal cellular prion protein with a methionine at position 129 has a more exposed helix 1 and is more prone to aggregate. / Pham, Nancy; Yin, Shaoman; Yu, Shuiliang; Wong, Poki; Kang, Shin Chung; Li, Chaoyang; Sy, Man Sun.
In: Biochemical and Biophysical Research Communications, Vol. 368, No. 4, 18.04.2008, p. 875-881.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Normal cellular prion protein with a methionine at position 129 has a more exposed helix 1 and is more prone to aggregate
AU - Pham, Nancy
AU - Yin, Shaoman
AU - Yu, Shuiliang
AU - Wong, Poki
AU - Kang, Shin Chung
AU - Li, Chaoyang
AU - Sy, Man Sun
PY - 2008/4/18
Y1 - 2008/4/18
N2 - The human prion gene, PRNP, has two allelic forms that encode either a methionine or valine at codon 129. This polymorphism strongly influences the pathogenesis of prion disease. However, the underlying mechanism remains unclear. We compared the conformation between wild-type human prion protein (rPrPC) with either a valine or methionine at position 129, using a panel of monoclonal antibodies that are specific for epitopes along the entire protein. We found that rPrPC(129M) has a more exposed helix 1 region compared to rPrPC(129V). Helix 1 is important in the aggregation process. Accordingly, rPrPC(129M) aggregates at a faster rate and forms more aggregate than rPrPC(129V). In addition, by using a rPrP with a pathogenic mutation of five additional octapeptide repeat insertions, rPrP(129M)/10OR, as "seeds", we showed that rPrP(129M)/10OR promotes the aggregation of rPrPC(129M) more efficiently than rPrPC(129V). These findings provide a possible mechanism underlying the influence of residue 129 on human prion disease.
AB - The human prion gene, PRNP, has two allelic forms that encode either a methionine or valine at codon 129. This polymorphism strongly influences the pathogenesis of prion disease. However, the underlying mechanism remains unclear. We compared the conformation between wild-type human prion protein (rPrPC) with either a valine or methionine at position 129, using a panel of monoclonal antibodies that are specific for epitopes along the entire protein. We found that rPrPC(129M) has a more exposed helix 1 region compared to rPrPC(129V). Helix 1 is important in the aggregation process. Accordingly, rPrPC(129M) aggregates at a faster rate and forms more aggregate than rPrPC(129V). In addition, by using a rPrP with a pathogenic mutation of five additional octapeptide repeat insertions, rPrP(129M)/10OR, as "seeds", we showed that rPrP(129M)/10OR promotes the aggregation of rPrPC(129M) more efficiently than rPrPC(129V). These findings provide a possible mechanism underlying the influence of residue 129 on human prion disease.
KW - Aggregation
KW - Epitope
KW - Polymorphism
KW - Prion protein
UR - http://www.scopus.com/inward/record.url?scp=40049100200&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40049100200&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.01.172
DO - 10.1016/j.bbrc.2008.01.172
M3 - Article
C2 - 18275852
AN - SCOPUS:40049100200
VL - 368
SP - 875
EP - 881
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -