{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Safar JG"],"funding":["NIA NIH HHS","NCRR NIH HHS","NINDS NIH HHS"],"pagination":["11312-7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC1544083"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["103(30)"],"pubmed_abstract":["Prions are composed solely of an alternatively folded isoform of the prion protein (PrP), designated PrP(Sc). The polyoxometalate phosphotungstic acid has been used to separate PrP(Sc) from its precursor PrP(C) by selective precipitation; notably, native PrP(Sc) has not been solubilized by using nondenaturing detergents. Because of the similarities between PrP(Sc) 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 (CJD) 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 PrP(Sc) through a highly cooperative process. Approximately 50% of the PrP(Sc) 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) PrP(Sc) or denatured recombinant HuPrP(90-231) for apoB and LDL ranged from 28 to 212 pM. Whether detection of PrP(Sc) 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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Human prions and plasma lipoproteins."],"pmcid":["PMC1544083"],"funding_grant_id":["P01 AG019724","K23 AG021989","AG021601","P01 AG010770","N01NS02328","AG02132","P01 AG021601","RR00079","AG021989","P50 AG023501","AG23501","AG019724","M01 RR000079","P01 AG002132","AG010770"],"pubmed_authors":["Miller BL","Serban A","Safar JG","Legname G","Geschwind MD","Deering C","King DJ","Wille H","Dearmond SJ","Mahley RW","Prusiner SB","Latawiec D","Weisgraber KH"],"additional_accession":[]},"is_claimable":false,"name":"Human prions and plasma lipoproteins.","description":"Prions are composed solely of an alternatively folded isoform of the prion protein (PrP), designated PrP(Sc). The polyoxometalate phosphotungstic acid has been used to separate PrP(Sc) from its precursor PrP(C) by selective precipitation; notably, native PrP(Sc) has not been solubilized by using nondenaturing detergents. Because of the similarities between PrP(Sc) 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 (CJD) 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 PrP(Sc) through a highly cooperative process. Approximately 50% of the PrP(Sc) 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) PrP(Sc) or denatured recombinant HuPrP(90-231) for apoB and LDL ranged from 28 to 212 pM. Whether detection of PrP(Sc) 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.","dates":{"release":"2006-01-01T00:00:00Z","publication":"2006 Jul","modification":"2026-03-16T16:29:38.823Z","creation":"2019-03-27T01:45:45Z"},"accession":"S-EPMC1544083","cross_references":{"pubmed":["16849426"],"doi":["10.1073/pnas.0604021103"]}}