Misfolded α-synuclein amyloid fibrils are the principal components of Lewy bodies and neurites, hallmarks of Parkinson’s disease (PD). Here we present a high-resolution structure of an α-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by electron microscopy and X-ray fiber diffraction. Over 200 unique long-range distance restraints define a consensus structure with common amyloid features including parallel in-register β-sheets and hydrophobic core residues, but also substantial complexity, arising from diverse structural features: an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a novel, orthogonal Greek-key topology. These characteristics contribute to the robust propagation of this fibril form, as evidenced by structural similarity of early-onset PD mutants. The structure provides a framework for understanding the interactions of α-synuclein with other proteins and small molecules to diagnose and treat PD.

Self-assembled cylindrical particles of wild type and recombinant tobacco mosaic virus (TMV) were used as organic templates for the controlled deposition and organization of Pt, Au, or Ag nanoparticles. Chemical reduction of [PtCl 6 ] 2or [AuCl 4 ]complexes at acidic pH gave rise to the specific decoration of the external surface of wild-type TMV rods with metallic nanoparticles less than 10 nm in size. In contrast, photochemical reduction of Ag(I) salts at pH 7 resulted in nucleation and constrained growth of discrete Ag nanoparticles aligned within the 4 nm-wide internal channel. The number of encapsulated nanoparticles increased when Ag benzoate rather than Ag nitrate was used due to reduced supersaturation associated with the lower Ag/benzoate redox couple, which enhanced the surface-templating effect of the channel wall carboxylates compared with nucleation in solution. Similar experiments using a mutant TMV with reduced negative charge along the central cavity confirmed that glutamic and aspartate acid groups were involved in site-specific deposition. Our results suggest that it should be possible to prepare 1-D arrays for a wide range of inorganic quantum dots by molecular engineering of the internal and external surfaces of self-assembled TMV tubules.

The use of biological molecules, assemblies and systems in the development of inorganic materials synthesis continues to offer new and exciting alternatives to conventional synthetic strategies. [1] Biological templates, such as protein cages, [2,3] viroid capsules, [4] bacterial rhapidosomes, [5] S-layers, [6] multicellular superstructures, [7] biolipid cylinders, [8,9] and DNA, [10±13] have been utilized to direct the deposition, assembly, and patterning of inorganic nanoparticles and microstructures. In this paper, we report a new approach to the template-directed synthesis of inor-ganic±organic nanotubes using tobacco mosaic virus (TMV).TMV is a remarkably stable virion, remaining intact at temperatures up to 60 C and at pH values between 2 and 10. Each viral particle consists of 2130 identical protein subunits arranged in a helical motif around a single strand of RNA to produce a hollow protein tube, 300´18 nm in size, with a 4 nm-wide central channel. [14,15] The internal and external surfaces of the protein consist of repeated patterns of charged amino acid residues, such as glutamate, aspartate, arginine, and lysine. [16] In principle, these functionalities should offer a wide variety of nucleation sites for surface-controlled inorganic deposition, which, in association with the high thermal and pH stability, could be exploited in the synthesis of unusual materials such as high-aspect-ratio composites and protein-confined inorgan-ic nanowires. Here we show that TMV is a suitable template for reactions such as co-crystallization (CdS and PbS), oxidative hydrolysis (iron oxides), and sol-gel condensation (SiO 2 ) (Fig. 1). Fig. 1. Scheme showing routes for the synthesis of nanotube composites using TMV templates. Clockwise from top right: sol±gel condensation (silica); coprecipitation (PbS and CdS nanocrystals); oxidative hydrolysis (iron oxide).Specific nucleation of CdS on the surface of dispersed particles of TMV was achieved by exposing a buffered suspension of the virions in 10 mM CdCl 2 to H 2 S gas for up to 6 h. Transmission electron microscopy (TEM) revealed the presence of mineralized tubular structures, approximately 50 nm in width, which consisted of a 16 nm thick electrondense outer crust and a 18 nm diameter internal core (Fig. 2a). Energy dispersive X-ray (EDX) analysis confirmed the presence of cadmium and sulfur in individual filaments, and high resolution lattice images indicated that the inorganic coating consisted of disordered aggregates of crystalline CdS particles 5 nm in size (Fig. 2b). The lattice spacings were in agreement with those obtained by selected area electron diffraction (SAED) of individual mineralized tubules, which showed powder patterns (d-spacings 0.336 nm (111), 0.206 nm (220), 0.176 nm (311), 0.133 nm (331), 0.118 nm (422)), corresponding to CdS nanoparticles with the zinc-blende crystal structure. The results were therefore consistent with a relatively uniform coating of CdS nanocrystals on the external surface of the TMV template. Although nucleation of CdS withi...