Single-residue physicochemical characteristics kinetically partition membrane protein self-assembly and aggregation.

ABSTRACT: Ninety-five percent of all transmembrane proteins exist in kinetically trapped aggregation-prone states that have been directly linked to neurodegenerative diseases. Interestingly, the primary sequence almost invariably avoids off-pathway aggregate formation, by folding reliably into its native, thermodynamically stabilized structure. However, with the rising incidence of protein aggregation diseases, it is now important to understand the underlying mechanism(s) of membrane protein aggregation. Micromolecular physicochemical and biochemical alterations in the primary sequence that trigger the formation of macromolecular cross-β aggregates can be measured only through combinatorial spectroscopic experiments. Here, we developed spectroscopic thermal perturbation with 117 experimental variabl

SUBMITTER: Gupta A 

PROVIDER: S-EPMC6996891 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature