Metal ions and redox balance regulate distinct amyloid-like aggregation pathways of GAPR-1.

ABSTRACT: Members of the CAP superfamily (Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-Related 1 proteins) are characterized by the presence of a structurally conserved CAP domain. The common structure-function relationship of this domain is still poorly understood. In this study, we unravel specific molecular mechanisms modulating the quaternary structure of the mammalian CAP protein GAPR-1 (Golgi-Associated plant Pathogenesis-Related protein 1). Copper ions are shown to induce a distinct amyloid-like aggregation pathway of GAPR-1 in the presence of heparin. This involves an immediate shift from native multimers to monomers which are prone to form amyloid-like fibrils. The Cu²⁺-induced aggregation pathway is independent of a conserved metal-binding site and involves the

SUBMITTER: Sheng J 

PROVIDER: S-EPMC6803662 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature