The conformational dynamics of the flanking polyQ regions in the membrane-bound state of huntingtin exon 1

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an abnormal expansion of the polyglutamine (polyQ) repeat within the first exon of huntingtin protein (httex1). The membrane interaction of httex1 is critical for its self-assembly and toxicity. While initial studies were essentially focused on polyQ peptide-lipid interaction, recent evidence supports that both flanking polyQ regions [the N17 segment and proline-rich domain (PRD)] strongly modulate the httex1 aggregation at membrane surfaces.