title: Intramolecular versus intermolecular disulfide bonds in prion proteins.
abstract: Prion protein (PrP) is the major component of the partially protease-resistant aggregate that accumulates in mammals with transmissible spongiform encephalopathies. The two cysteines of the scrapie form, PrP(Sc), were found to be in their oxidized (i.e. disulfide) form (Turk, E., Teplow, D. B., Hood, L. E., and Prusiner, S. B. (1988) Eur. J. Biochem. 176, 21-30); however, uncertainty remains as to whether the disulfide bonds are intra- or intermolecular. It is demonstrated here that the monomers of PrP(Sc) are not linked by intermolecular disulfide bonds. Furthermore, evidence is provided that PrP(Sc) can induce the conversion of the oxidized, disulfide-intact form of the monomeric cellular prion protein to its protease-resistant form without the temporary breakage and subsequent re-formation of the disulfide bonds in cell-free reactions.
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.
authors.forename: Ervin
authors.initials: E
authors.lastname: Welker
authors.forename: Lynne D
authors.initials: LD
authors.lastname: Raymond
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
authors.forename: Byron
authors.initials: B
authors.lastname: Caughey
mesh_terms: D000818:Animals; D002474:Cell-Free System; D006224:Cricetinae; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019791:Guanidine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D010100:Oxygen / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D004220:Disulfides; D011328:Prions; D013438:Sulfhydryl Compounds; D019791:Guanidine; D003545:Cysteine; D010100:Oxygen