Global profiling of protein complex dynamics with an experimental library of protein interaction markers.

Methods to systematically monitor protein complex dynamics are needed. We introduce serial ultrafiltration combined with limited proteolysis-coupled mass spectrometry (FLiP-MS), a structural proteomics workflow that generates a library of peptide markers specific to changes in PPIs by probing differences in protease susceptibility between complex-bound and monomeric forms of proteins. The library includes markers mapping to protein-binding interfaces and markers reporting on structural changes that accompany PPI changes.

Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington's disease.

Huntington's disease (HD) is a late onset, inherited neurodegenerative disorder for which early pathogenic events remain poorly understood. Here we show that mutant exon 1 HTT proteins are recruited to a subset of cytoplasmic aggregates in the cell bodies of neurons in brain sections from presymptomatic HD, but not wild-type, mice. This occurred in a disease stage and polyglutamine-length dependent manner.

A Liquid to Solid Phase Transition Underlying Pathological Huntingtin Exon1 Aggregation.

Huntington'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.

Exploiting In Situ Solid-State NMR for the Discovery of New Polymorphs during Crystallization Processes.

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.