Enhanced accessibility and hydrophobicity of amyloidogenic intermediates of the β2-microglobulin D76N mutant revealed by high-pressure experiments.

ABSTRACT: β2-Microglobulin (β2m) is the causative protein of dialysis-related amyloidosis. Its unfolding mainly proceeds along the pathway of N_C →U_C ⇄ U_T, whereas refolding follows the U_T → I_T (→N_T) →N_C pathway, in which N, I, and U are the native, intermediate, and unfolded states, respectively, with the Pro32 peptidyl-prolyl bond in cis or trans conformation as indicated by the subscript. It is noted that the I_T state is a putative amyloidogenic precursor state. Several aggregation-prone variants of β2m have been reported to date. One of these variants is D76N β2m, which is a naturally occurring amyloidogenic mutant. To elucidate the molecular mechanisms contributing to the enhanced amyloidogenicity of the muta

SUBMITTER: Sakurai K 

PROVIDER: S-EPMC7950326 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature