Structural insights into immunoglobulin M

  • Science. 2020 Feb 28;367(6481):1014-1017. doi: 10.1126/science.aaz5425.
Yaxin Li  1  2 ,  Guopeng Wang  3 ,  Ningning Li  2  3 ,  Yuxin Wang  1  2 ,  Qinyu Zhu  1  2 ,  Huarui Chu  1  2 ,  Wenjun Wu  4  5 ,  Ying Tan  4  5 ,  Feng Yu  4  5  6 ,  Xiao-Dong Su  1 ,  Ning Gao  2  3 ,  Junyu Xiao  7  2
Affiliations
  • 1. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
  • 2. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 3. State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.
  • 4. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
  • 5. Institute of Nephrology, Peking University, Beijing, China.
  • 6. Department of Nephrology, Peking University International Hospital, Beijing, China.
  • 7. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. [email protected].
PMID: 32029689 DOI: 10.1126/science.aaz5425
Abstract

Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo-electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM.