SUNY at Albany
June 19-23, 2001
Nmr Studies of Structures And Mechanisms in Biological Systems
The "protein-only hypothesis" suggests that onset of transmissible spongiform encephalopathies (TSE), such as scrapie in sheep, bovine spongiform encephaolpathy (BSE) and Creutzfeldt-Jakob disease (CJD) in humans is related to a conformational transition of the ubiq-uitous cellular form of the prion protein in mammalian tissues, PrPC, into a disease-related form, PrPSc. In this situation, knowledge on the three-dimensional structures of prion proteins, and possibly of related proteins, is of keen interest. Nuclear magnetic resonance (NMR) spectros-copy has so far been the only technique capable of solving three-dimensional structures of mam-malian prion proteins at atomic resolution. Presently, NMR structures are available for the intact recombinant prion proteins of humans, cattle, the mouse and the Syrian hamster, as well as for a variety of PrP homologs and PrP fragments from these four species. NMR structures of the human and murine doppel proteins are also available. All these structures appear to represent monomeric, water-soluble forms of the proteins, and their comparison will then be used as a ba-sis for a discussion of possible rationales for implicated roles of PrP in the development of prion diseases, and in particular for the species barrier observed in infectious transmission of TSEs.
In an outlook to the future, special consideration will be given to new techniques (TROSY, CRINEPT) that enable solution NMR studies with much larger structures than have hitherto been investigated using conventional NMR techniques. Initial applications of these techniques with membrane proteins will be described.
Institut für Molekullarbiologie und Biophysik, Eidgenössische Technische
Hochschule, CH-8093 Zurich, Switzerland