Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design.

ABSTRACT: Inhibiting the interaction between amyloid-β (Aβ) and a neuronal cell surface receptor, LilrB2, has been suggested as a potential route for treating Alzheimer's disease. Supporting this approach, Alzheimer's-like symptoms are reduced in mouse models following genetic depletion of the LilrB2 homologue. In its pathogenic, oligomeric state, Aβ binds to LilrB2, triggering a pathway to synaptic loss. Here we identify the LilrB2 binding moieties of Aβ (¹⁶KLVFFA²¹) and identify its binding site on LilrB2 from a crystal structure of LilrB2 immunoglobulin domains D1D2 complexed to small molecules that mimic phenylalanine residues. In this structure, we observed two pockets that can accommodate the phenylalanine side chains of KLVFFA. These pockets were confirmed to be ^16<

SUBMITTER: Cao Q 

PROVIDER: S-EPMC6250578 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature