투고논문

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.

Keywords huntingtin protein, Huntington’s disease, NMR, amyloid fibril, aggregation

*Address correspondence to: Min-Duk Seo, College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi 16499, Republic of Korea, Tel: 82-31-219-; E-mail: mdseo@ajou.ac.kr