title: pH-Dependent recognition of apoptotic and necrotic cells by the human dendritic cell receptor DEC205.
abstract: Dendritic cells play important roles in regulating innate and adaptive immune responses. DEC205 (CD205) is one of the major endocytotic receptors on dendritic cells and has been widely used for vaccine generation against viruses and tumors. However, little is known about its structure and functional mechanism. Here we determine the structure of the human DEC205 ectodomain by cryoelectron microscopy. The structure shows that the 12 extracellular domains form a compact double ring-shaped conformation at acidic pH and become extended at basic pH. Biochemical data indicate that the pH-dependent conformational change of DEC205 is correlated with ligand binding and release. DEC205 only binds to apoptotic and necrotic cells at acidic pH, whereas live cells cannot be recognized by DEC205 at either acidic or basic conditions. These results suggest that DEC205 is an immune receptor that recognizes apoptotic and necrotic cells specifically through a pH-dependent mechanism.
authors.affiliation: National Center for Protein Science, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;
authors.forename: Longxing
authors.initials: L
authors.lastname: Cao
authors.affiliation: National Center for Protein Science, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Shi
authors.affiliation: National Center for Protein Science, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;
authors.forename: Haishuang
authors.initials: H
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Qinfen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Center for Protein Science, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China; he@sibcb.ac.cn.
authors.forename: Yongning
authors.initials: Y
authors.lastname: He
mesh_terms: D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D003713:Dendritic Cells / Q000166:cytology*; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D015778:Minor Histocompatibility Antigens; D016296:Mutagenesis; D009336:Necrosis; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface
keywords: DEC205; apoptosis; cryoEM; mannose receptor family; pH dependence