Effect of pH on the Structure and Fibrillation Propensity of Huntingtin Exon-1 17Q
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Huntingtin exon 1 (HttEx1) is a key fragment associated with Huntington’s disease (HD), whose conformational behavior that is strongly influenced by environmental conditions. Here, we investigated the pH-dependent conformational and aggregation behavior of non-pathogenic HttEx1-17Q using thioflavin T (ThT) fluorescence, circular dichroism (CD), and solution nuclear magnetic resonance (NMR) spectroscopy. Although pathogenic polyQ-expanded huntingtin has been extensively studied, non-pathogenic HttEx1 remains comparatively unexplored. In particular, protonation- driven effects on the monomeric conformational ensemble and association processes of HttEx1-17Q have not been fully clarified. In this work, we provide characterization of pH-dependent structural and dynamic features of HttEx1-17Q in solution.
Abstract
Huntingtin exon 1 (HttEx1) is a key fragment associated with Huntington’s disease (HD), whose conformational behavior that is strongly influenced by environmental conditions. Here, we investigated the pH-dependent conformational and aggregation behavior of non-pathogenic HttEx1-17Q using thioflavin T (ThT) fluorescence, circular dichroism (CD), and solution nuclear magnetic resonance (NMR) spectroscopy. Although pathogenic polyQ-expanded huntingtin has been extensively studied, non-pathogenic HttEx1 remains comparatively unexplored. In particular, protonation- driven effects on the monomeric conformational ensemble and association processes of HttEx1-17Q have not been fully clarified. In this work, we provide characterization of pH-dependent structural and dynamic features of HttEx1-17Q in solution.