Effects of Macromolecular Cosolutes on the Kinetics of Huntingtin Aggregation Monitored by NMR Spectroscopy.

ABSTRACT: The effects of two macromolecular cosolutes, specifically the polysaccharide dextran-20 and the protein lysozyme, on the aggregation kinetics of a pathogenic huntingtin exon-1 protein (hht^ex1) with a 35 polyglutamine repeat, htt^ex1Q₃₅, are described. A unified kinetic model that establishes a direct connection between reversible tetramerization occurring on the microsecond time scale and irreversible fibril formation on a time scale of hours/days forms the basis for quantitative analysis of htt^ex1Q₃₅ aggregation, monitored by measuring cross-peak intensities in a series of 2D ¹H-¹⁵N NMR correlation spectra acquired during the course of aggregation. The primary effects of the two cosolutes are associated with shift

SUBMITTER: Torricella F 

PROVIDER: S-EPMC11345868 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature