title: Prion protein NMR structure and species barrier for prion diseases.
abstract: The structural basis of species specificity of transmissible spongiform encephalopathies, such as bovine spongiform encephalopathy or "mad cow disease" and Creutzfeldt-Jakob disease in humans, has been investigated using the refined NMR structure of the C-terminal domain of the mouse prion protein with residues 121-231. A database search for mammalian prion proteins yielded 23 different sequences for the fragment 124-226, which display a high degree of sequence identity and show relevant amino acid substitutions in only 18 of the 103 positions. Except for a unique isolated negative surface charge in the bovine protein, the amino acid differences are clustered in three distinct regions of the three-dimensional structure of the cellular form of the prion protein. Two of these regions represent potential species-dependent surface recognition sites for protein-protein interactions, which have independently been implicated from in vitro and in vivo studies of prion protein transformation. The third region consists of a cluster of interior hydrophobic side chains that may affect prion protein transformation at later stages, after initial conformational changes in the cellular protein.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, CH-8093 Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Billeter
authors.forename: R
authors.initials: R
authors.lastname: Riek
authors.forename: G
authors.initials: G
authors.lastname: Wider
authors.forename: S
authors.initials: S
authors.lastname: Hornemann
authors.forename: R
authors.initials: R
authors.lastname: Glockshuber
authors.forename: K
authors.initials: K
authors.lastname: Wüthrich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D017096:Prion Diseases / Q000635:transmission*; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D013045:Species Specificity
chemical_list: D011328:Prions