LilrB3 is a putative cell surface receptor of APOE4.

ABSTRACT: The three isoforms of apolipoprotein E (APOE2, APOE3, and APOE4) only differ in two amino acid positions but exert quite different immunomodulatory effects. The underlying mechanism of such APOE isoform dependence remains enigmatic. Here we demonstrate that APOE4, but not APOE2, specifically interacts with the leukocyte immunoglobulin-like receptor B3 (LilrB3). Two discrete immunoglobin-like domains of the LilrB3 extracellular domain (ECD) recognize a positively charged surface patch on the N-terminal domain (NTD) of APOE4. The atomic structure reveals how two APOE4 molecules specifically engage two LilrB3 molecules, bringing their intracellular signaling motifs into close proximity through formation of a hetero-tetrameric complex. Consistent with our biochemical and structural analyses, A

SUBMITTER: Zhou J 

PROVIDER: S-EPMC9892561 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature