title: The configuration of the Cu(2+) binding region in full-length human prion protein compared with the isolated octapeptide.
abstract: The cellular prion protein (PrP(C)) is a copper binding protein. The molecular features of the Cu(2+) binding sites have been investigated and characterized by spectroscopic experiments on PrP(C)-derived peptides and the correctly folded human full-length PrP(C) (hPrP-[23-231]). These experiments allowed us to distinguish two different configurations of copper binding. The different copper complexes depend on sequence context, buffer conditions and stoichiometry of copper. The combined information of spectroscopic data from our EXAFS, EPR and ENDOR experiments was used to create models for these two copper complexes. A large number of conformations of these models were calculated using molecular mechanics computations, and the simulated spectra of these structures were compared with our experimental data. Common features and differences of the copper binding motifs are discussed in this paper and it remains for future investigations to study whether different configurations are associated with different functional states of PrP(C).
authors.affiliation: Physics Department E17, Technical University Munich, D-85747 Garching, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weiss
authors.forename: Pablo
authors.initials: P
authors.lastname: Del Pino
authors.forename: Uwe
authors.initials: U
authors.lastname: Bertsch
authors.forename: Christian
authors.initials: C
authors.lastname: Renner
authors.forename: Matthias
authors.initials: M
authors.lastname: Mentler
authors.forename: Klaus
authors.initials: K
authors.lastname: Grantner
authors.forename: Luis
authors.initials: L
authors.lastname: Moroder
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Fritz G
authors.initials: FG
authors.lastname: Parak
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013052:Spectrometry, X-Ray Emission / Q000379:methods
chemical_list: D002352:Carrier Proteins; D046912:Multiprotein Complexes; D011328:Prions; C023548:copper-binding protein; D003300:Copper