Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-? fibrils.

ABSTRACT: Misfolding of Amyloid ? (A?) peptides leads to the formation of extracellular amyloid plaques. Molecular chaperones can facilitate the refolding or degradation of such misfolded proteins. Here, for the first time, we report the unique ability of Lipocalin-type Prostaglandin D synthase (L-PGDS) protein to act as a disaggregase on the pre-formed fibrils of A?(1-40), abbreviated as A?40, and A?(25-35) peptides, in addition to inhibiting the aggregation of A? monomers. Furthermore, our proteomics results indicate that L-PGDS can facilitate extraction of several other proteins from the insoluble aggregates extracted from the brain of an Alzheimer's disease patient. In this study, we have established the mode of binding of L-PGDS with monomeric and fibrillar A? using Nuclear Magnetic Resonance (NMR) Spectroscopy, Small Angle X-ray Scattering (SAXS), and Transmission Electron Microscopy (TEM). Our results confirm a direct interaction between L-PGDS and monomeric A?40 and A?(25-35), thereby inhibiting their spontaneous aggregation. The monomeric unstructured A?40 binds to L-PGDS via its C-terminus, while the N-terminus remains free which is observed as a new domain in the L-PGDS-A?40 complex model.

SUBMITTER: Kannaian B 

PROVIDER: S-EPMC6715741 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature