TY - JOUR
T1 - Novel Differences between Two Human Prion Strains Revealed by Two-dimensional Gel Electrophoresis
AU - Pan, Tao
AU - Colucci, Monica
AU - Wong, Boon Seng
AU - Li, Ruliang
AU - Liu, Tong
AU - Petersen, Robert B.
AU - Chen, Shu
AU - Gambetti, Pierluigi
AU - Sy, Man Sun
PY - 2001/10/5
Y1 - 2001/10/5
N2 - The phenotype of human sporadic prion diseases is affected by patient genotype at codon 129 of the prion protein (PrP) gene, the site of a common methionine/valine polymorphism, and by the type of the scrapie PrP (PrP Sc), which likely reflects the prion strain. However, two distinct disease phenotypes, identified as sporadic Creutzfeldt-Jakob disease (M/M2 sCJD) and sporadic fatal insomnia (sFI), share methionine homozygosity at codon 129 and PrPSc type 2. One-dimensional gel electrophoresis and immunoblotting reveal no difference between the M/M2 sCJD and sFI species of PrPSc in gel mobility and glycoform ratio. In contrast, the two-dimensional immunoblot demonstrates that in M/M2 sCJD the full-length PrPSc form is overrepresented and carries glycans that are different from those present in the PrPSc of sFI. Because the altered glycans are detectable only in the PrPSc and not in the normal or cellular PrP (PrPC), they are likely to result from preferential conversion to PrPSc of rare PrPC glycoforms. This is the first evidence that a qualitative difference in glycans contributes to prion diversity.
AB - The phenotype of human sporadic prion diseases is affected by patient genotype at codon 129 of the prion protein (PrP) gene, the site of a common methionine/valine polymorphism, and by the type of the scrapie PrP (PrP Sc), which likely reflects the prion strain. However, two distinct disease phenotypes, identified as sporadic Creutzfeldt-Jakob disease (M/M2 sCJD) and sporadic fatal insomnia (sFI), share methionine homozygosity at codon 129 and PrPSc type 2. One-dimensional gel electrophoresis and immunoblotting reveal no difference between the M/M2 sCJD and sFI species of PrPSc in gel mobility and glycoform ratio. In contrast, the two-dimensional immunoblot demonstrates that in M/M2 sCJD the full-length PrPSc form is overrepresented and carries glycans that are different from those present in the PrPSc of sFI. Because the altered glycans are detectable only in the PrPSc and not in the normal or cellular PrP (PrPC), they are likely to result from preferential conversion to PrPSc of rare PrPC glycoforms. This is the first evidence that a qualitative difference in glycans contributes to prion diversity.
UR - http://www.scopus.com/inward/record.url?scp=0035813151&partnerID=8YFLogxK
U2 - 10.1074/jbc.M107358200
DO - 10.1074/jbc.M107358200
M3 - Article
C2 - 11489910
AN - SCOPUS:0035813151
VL - 276
SP - 37284
EP - 37288
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 40
ER -