Characterization of β-sheet structure in Ure2p1- 89 yeast prion fibrils by solid-state nuclear magnetic resonance

Residues 1−89 constitute the Asn- and Gln-rich segment of the Ure2p protein and produce the [URE3] prion of Saccharomyces cerevisiae by forming the core of intracellular Ure2p amyloid. We report the results of solid-state nuclear magnetic resonance (NMR) measurements that probe the molecular structure of amyloid fibrils formed by Ure2p1-89 in vitro. Data include measurements of intermolecular magnetic dipole−dipole couplings in samples that are 13C-labeled at specific sites and two-dimensional 15N−13C and 13C−13C NMR spectra of samples that are uniformly 15N- and 13C-labeled. Intermolecular dipole−dipole couplings indicate that the β-sheets in Ure2p1-89 fibrils have an in-register parallel structure. An in-register parallel β-sheet structure permits polar zipper interactions among side chains of Gln and Asn residues and explains the tolerance of [URE3] to scrambling of the sequence in residues 1−89. Two-dimensional NMR spectra of uniformly labeled Ure2p1-89 fibrils, even when fully hydrated, show NMR line...