The amyloid fibrils of beta-amyloid (Aβ) peptides play important roles in the pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled Aβ assemblies have been hampered for a long time by sample heterogeneity and low spectral resolution. In this work, SSNMR studies on well-ordered fibril samples of Aβ(40) with an additional N-terminal methionine provide high-resolution spectra which lead to an accurate structural model. The fibrils studied here carry distinct structural features compared to previous reports. The inter-β-strand contacts within the U-shaped β-strand-turn-β-strand motif are shifted, the N-terminal region adopts a β-conformation, and new inter-monomer contacts occur at the protofilament interface. The revealed structural diversity in Aβ fibrils points to a complex picture of Aβ fibrillation.

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The solution structure of oxidized horse heart cytochrome c was obtained at pH 7.0 in 100 mM phosphate buffer from 2278 NOEs and 241 pseudocontact shift constraints. The final structure was refined through restrained energy minimization. A 35-member family, with RMSD values with respect to the average structure of 0.70 ( 0.11 Å and 1.21 ( 0.14 Å for the backbone and all heavy atoms, respectively, and with an average penalty function of 130 ( 4.0 kJ/mol and 84 ( 3.7 kJ/mol for NOE and pseudocontact shift constraints, respectively (corresponding to a target function of 0.9 Å 2 and 0.2 Å 2 ), was obtained. The solution structure is somewhat different from that recently reported (Qi et al., 1996) and appears to be similar to the X-ray structure of the same oxidation state (Bushnell et al., 1990). A noticeable difference is a rotation of 17 ( 8°of the imidazole plane between solid and solution structure. Detailed and accurate structural determinations are important within the frame of the current debate of the structural rearrangements occurring upon oxidation or reduction. From the obtained magnetic susceptibility tensor a separation of the hyperfine shifts into their contact and pseudocontact contributions is derived and compared to that of the analogous isoenzyme from S. cereVisiae and to previous results.