SummaryHuntington’s disease is caused by an abnormally long polyglutamine tract in the huntingtin protein. This leads to the generation and deposition of N-terminal exon1 fragments of the protein in intracellular aggregates. We combined electron tomography and quantitative fluorescence microscopy to analyze the structural and material properties of huntingtin exon1 assemblies in mammalian cells, in yeast, and in vitro. We found that huntingtin exon1 proteins can form reversible liquid-like assemblies, a process driven by huntingtin’s polyQ tract and proline-rich region. In cells and in vitro, the liquid-like assemblies converted to solid-like assemblies with a fibrillar structure. Intracellular phase transitions of polyglutamine proteins could play a role in initiating irreversible pathological aggregation.
Members of a homologous family of 1:2 cocrystals comprising even-chain α,ω-dihydroxyalkanes and urea have been reported previously to fall into three well-defined structure types, although surprisingly polymorphism was not observed for any member of this series. Here we report the discovery of the first examples of polymorphism within this family of materials, specifically for 1,6-dihydroxyhexane-(urea) 2 and 1,8-dihydroxyoctane-(urea) 2 . The new polymorphs have been prepared by mechanochemical milling, and the crystal structures have been determined directly from powder X-ray diffraction data. On the basis of periodic density functional theory calculations, the new polymorphs are assigned as metastable with respect to the polymorphs reported previously. Under ambient conditions, the new polymorph of 1,6-dihydroxyhexane-(urea) 2 transforms to the previously known polymorph over a matter of days. However, the new polymorph of 1,8-dihydroxyoctane-(urea) 2 has significantly greater kinetic stability, which can be rationalized on the basis of the specific structural reorganization required to transform to the previously known polymorph.
We report the discovery of new polymorphic forms of solids by exploiting a solid-state NMR technique that has been developed for in situ monitoring of the evolution of crystallization processes. The capability of the technique to reveal the existence of new polymorphic forms of molecular solids is illustrated by the discovery of two new polymorphs of methyldiphenylphosphine oxide and a new solid form of the 1,10-dihydroxydecane/urea system.
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