Cryo-EM structure of the human IgM B cell receptor

被引:49
作者
Su, Qiang [1 ,2 ]
Chen, Mengying [3 ]
Shi, Yan [1 ,2 ,4 ]
Zhang, Xiaofeng [1 ,2 ]
Huang, Gaoxingyu [1 ,2 ]
Huang, Bangdong [1 ,2 ]
Liu, Dongwei [4 ]
Liu, Zhangsuo [4 ]
Shi, Yigong [1 ,2 ,3 ]
机构
[1] Westlake Univ, Res Ctr Ind Future, Sch Life Sci, Inst Biol,Westlake Inst Adv Study,Key Lab Struct, Hangzhou 310024, Zhejiang, Peoples R China
[2] Westlake Lab Life Sci & Biomed, Hangzhou 310024, Zhejiang, Peoples R China
[3] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Tsinghua Peking Joint Ctr Life Sci, Sch Life Sci,Sch Med, Beijing 100084, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Henan Prov Res Ctr Kidney Dis, Dept Integrated Tradit & Western Nephrol, Zhengzhou 450052, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
ANTIGEN RECEPTOR; CRYSTAL-STRUCTURE; ORGANIZATION; INITIATION; ALPHA; BETA;
D O I
10.1126/science.abo3923
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
07 ; 0710 ; 09 ;
摘要
The B cell receptor (BCR) initiates immune responses through antigen recognition. We report a 3.3-angstrom cryo-electron microscopy structure of human immunoglobulin M (IgM)-BCR in the resting state. IgM-BCR comprises two heavy chains, two light chains, and the Ig alpha/Ig beta heterodimer. The ectodomains of the heavy chains closely stack against those of Ig alpha/Ig beta, with one heavy chain locked between Ig alpha and Ig beta in the juxtamembrane region. Extracellular interactions may determine isotype specificity of the BCR. The transmembrane helices of IgM-BCR form a four-helix bundle that appears to be conserved among all BCR isotypes. This structure contains 14 glycosylation sites on the IgM-BCR ectodomains and reveals three potential surface binding sites. Our work reveals the organizational principles of the BCR and may facilitate the design of antibody-based therapeutics.
引用
收藏
页码:875 / +
页数:6
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