pH-dependent recognition of apoptotic and necrotic cells by the human dendritic cell receptor DEC205

被引：46

作者：

Cao, Longxing ^{[1
]}

Shi, Xiangyi ^{[1
]}

Chang, Haishuang ^{[1
]}

Zhang, Qinfen ^{[2
]}

He, Yongning ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci,State Key Lab Mol Biol, Shanghai 201210, Peoples R China

[2] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 23期

基金：

中国国家自然科学基金;

关键词：

DEC205; pH dependence; apoptosis; cryoEM; mannose receptor family; MANNOSE RECEPTOR; IMMUNE-RESPONSES; IN-VIVO; EXTRACELLULAR ACIDOSIS; ELECTRON-MICROSCOPY; CLEARANCE; DEC-205; INNATE; PHAGOCYTOSIS; ANTIGENS;

D O I：

10.1073/pnas.1505924112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：7237 / 7242

页数：6

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