Acquired Disorder and Asymmetry in a Domain-Swapped Model for γ-Crystallin Aggregation.

ABSTRACT: Misfolding and aggregation of proteins occur in many pathological states. Because of the inherent disorder involved, these processes are difficult to study. We attempted to capture aggregation intermediates of γS-crystallin, a highly stable, internally symmetrical monomeric protein, by crystallization under mildly acidic and oxidizing conditions. Here we describe novel oligomerization through strained domain-swapping and partial intermolecular disulfide formation. This forms an octamer built from asymmetric tetramers, each of which comprises an asymmetric pair of twisted, domain-swapped dimers. Each tetramer shows patterns of acquired disorder among subunits, ranging from local loss of secondary structure to regions of intrinsic disorder. The octamer ring is tied together by partial interm

SUBMITTER: Sagar V 

PROVIDER: S-EPMC9050881 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature