Pathogenic D76N Variant of β₂-Microglobulin: Synergy of Diverse Effects in Both the Native and Amyloid States.

ABSTRACT: β₂-microglobulin (β2m), the light chain of the MHC-I complex, is associated with dialysis-related amyloidosis (DRA). Recently, a hereditary systemic amyloidosis was discovered, caused by a naturally occurring D76N β2m variant, which showed a structure remarkably similar to the wild-type (WT) protein, albeit with decreased thermodynamic stability and increased amyloidogenicity. Here, we investigated the role of the D76N mutation in the amyloid formation of β2m by point mutations affecting the Asp76-Lys41 ion-pair of WT β2m and the charge cluster on Asp38. Using a variety of biophysical techniques, we investigated the conformational stability and partial unfolding of the native state of the variants, as well as their amyloidogenic propensity and the stability of amyloid fibrils un

SUBMITTER: Bulyaki E 

PROVIDER: S-EPMC8614874 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature