期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 30, 页码 11312-11317出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0604021103
关键词
prion protein; apolipoprotein B; blood; Creutzfeldt-Jakob disease
资金
- NCRR NIH HHS [RR00079, M01 RR000079] Funding Source: Medline
- NIA NIH HHS [P01 AG002132, AG021601, P01 AG019724, K23 AG021989, AG019724, AG010770, P01 AG021601, P01 AG010770, AG021989, AG02132, AG23501, P50 AG023501] Funding Source: Medline
- NINDS NIH HHS [N01NS02328] Funding Source: Medline
Prions are composed solely of an alternatively folded isoform of the prion protein (PrP), designated PrPSc. The polyoxometalate phosphotungstic acid has been used to separate PrPSc from its precursor PrPC by selective precipitation; notably, native PrPSc has not been solubilized by using nondenaturing detergents. Because of the similarities between PrPSc and lipoproteins with respect to hydrophobicity and formation of phosphotungstic acid complexes, we asked whether these molecules are bound to each other in blood. Here we report that prions from the brains of patients with sporadic Creutzfeldt-Jakob disease (OD) bind to very low-density (VLDL) and low-density (LDL) lipoproteins but not to high-density lipoproteins (HDL) or other plasma components, as demonstrated both by affinity assay and electron microscopy. Immunoassays demonstrated that apolipoprotein B (apoB), which is the major protein component of VLDL and LDL, bound PrPSc through a highly cooperative process. Approximately 50% of the PrPSc bound to LDL particles was released after exposure to 4 M guanidine hydrochloride at 80 degrees C for 20 min. The apparent binding constants of native human (Hu) PrPSc or denatured recombinant HuPrP(90-231) for apoB and LDL ranged from 28 to 212 pM. Whether detection of PrPSc in VLDL and LDL particles can be adapted into an antemortem diagnostic test for prions in the blood of humans, livestock, and free-ranging cervids remains to be determined.
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