LilrB3 is a putative cell surface receptor of APOE4  

作　　者：Jiayao Zhou Yumeng Wang Gaoxingyu Huang Min Yang Yumin Zhu Chen Jin Dan Jing Kai Ji Yigong Shi 

机构地区：[1]Key Laboratory of Structural Biology of Zhejiang Province,School of Life Sciences,Westlake University,Institute of Biology,Westlake Institute for Advanced Study,Hangzhou,Zhejiang,China [2]Zhejiang Provincial Laboratory of Life Sciences and Biomedicine,Hangzhou,Zhejiang,China [3]Advanced Research Center for Biological Structure&Beijing Advanced Innovation Center for Structural Biology,Tsinghua-Peking Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China [4]Department of Maternal,Child&Adolescent Health,School of Public Health,Anhui Medical University,MOE Key Laboratory of Population Health Across Life Cycle,Anhui Provincial Key Laboratory of Population Health and Aristogenics,Hefei,Anhui,China

出　　处：《Cell Research》2023年第2期116-130,共15页细胞研究（英文版）

基　　金：National Key R&D Program of China(2020YFA0509300 to Y.S.);National Natural Science Foundation of China(81920108015 to Y.S.);Key R&D Program of Zhejiang Province(2020C04001 to Y.S.);Start-up funds from Westlake University.

摘　　要：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,APOE4,but not APOE2,activates human microglia cells(HMC3)into a pro-inflammatory state in a LilrB3-dependent manner.Together,our study identifies LilrB3 as a putative immune cell surface receptor for APOE4,but not APOE2,and may have implications for understanding the biological functions as well as disease relevance of the APOE isoforms.

关 键 词：SURFACE bringing APOE 

分 类 号：Q2[生物学—细胞生物学]