title: NMR structure of a variant human prion protein with two disulfide bridges.
abstract: The nuclear magnetic resonance structure of the globular domain with residues 121-230 of a variant human prion protein with two disulfide bonds, hPrP(M166C/E221C), shows the same global fold as wild-type hPrP(121-230). It contains three alpha-helices of residues 144-154, 173-194 and 200-228, an anti-parallel beta-sheet of residues 128-131 and 161-164, and the disulfides Cys166-Cys221 and Cys179-Cys214. The engineered extra disulfide bond in the presumed "protein X"-binding site is accommodated with slight, strictly localized conformational changes. High compatibility of hPrP with insertion of a second disulfide bridge in the protein X epitope was further substantiated by model calculations with additional variant structures. The ease with which the hPrP structure can accommodate a variety of locations for a second disulfide bond within the presumed protein X-binding epitope suggests a functional role for the extensive perturbation by a natural second disulfide bond of the corresponding region in the human doppel protein.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Zürich, CH-8093, Zurich, Switzerland. rz@mol.biol.ethz.ch
authors.forename: Ralph
authors.initials: R
authors.lastname: Zahn
authors.forename: Peter
authors.initials: P
authors.lastname: Güntert
authors.forename: Christine
authors.initials: C
authors.lastname: von Schroetter
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry*; D058851:GPI-Linked Proteins; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011328:Prions / Q000737:chemistry* / Q000235:genetics*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012984:Software; D013816:Thermodynamics
chemical_list: D004220:Disulfides; D058851:GPI-Linked Proteins; C501125:PRND protein, human; D011328:Prions