Structure of Human M-type Phospholipase A2 Receptor Revealed by Cryo-Electron Microscopy. Issue 24 (8th December 2017)

• Record Type: Journal Article
• Authors: Dong, Yue; Cao, Longxing; Tang, Hua; Shi, Xiangyi; He, Yongning
• Is Part Of: Journal of molecular biology. Volume 429:Issue 24(2017)
• Page Start: 3825
• Page End: 3835
• Publication Date: 2017-12-08
• Subjects: sPLA2s secretory phospholipase A2s -- M-PLA2R M-type phospholipase A2 receptor -- CysR cysteine-rich domain -- FNII fibronectin type II domain -- CTLDs C-type lectin-like domains -- IMN idiopathic membranous nephropathy -- SEC size-exclusion chromatography -- cryoEM cryo-electron microscopy; M-PLA2R -- CryoEM -- Mannose receptor family -- pH-dependent -- Membranous nephropathy; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.10.019
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: M-type phospholipase A2 receptor (M-PLA2R) is a member of the mannose receptor family and known as the receptor of secretory phospholipase A2s. It has also been identified as the major autoantigen of idiopathic membranous nephropathy, one of the most common causes for nephrotic syndrome in adults. Here we determine the structure of human M-PLA2R ectodomain by cryo-electron microscopy. The results show that the ectodomain has high internal flexibility and forms a compact dual-ring-shaped conformation at acidic pH and adopts extended conformations at basic pH. The inter-domain interactions of human M-PLA2R are explored by the binding studies with individual domains, showing the mechanism of the conformational change. In addition, the biochemical data suggest that mouse M-PLA2R recognizes mouse secretory phospholipase A2-G1B only at physiological or basic pH, rather than at acidic pH. These results suggest that the pH-dependent conformational change might play important roles in the functional activities of M-PLA2R such as ligand binding and release, and may also be relevant to the immunogenicity in membranous nephropathy. Graphical abstract: Highlights: The structure of human M-PLA2R by cryoEM Dual-ring-shaped conformation of human M-PLA2R at acidic pH pH-dependent conformational change of M-PLA2R pH-dependent recognition of mouse M-PLA2R with its ligand Potential locations of the epitopes for IMN autoantibodies