Structural insights into immunoglobulin M

Area of Science:

• Structural Biology
• Immunology
• Molecular Mechanisms

Background:

• Immunoglobulin M (IgM) is crucial for humoral and mucosal immunity.
• The assembly and transport of IgM involve the joining chain (J-chain) and polymeric immunoglobulin receptor (pIgR).
• Molecular mechanisms underlying IgM assembly and transport remain poorly understood.

Purpose of the Study:

• To elucidate the structural basis of IgM assembly and transport.
• To determine the molecular interactions between IgM-Fc, J-chain, and pIgR ectodomain.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to visualize the complex.
• Structural analysis of the human IgM-Fc region in complex with J-chain and pIgR ectodomain.

Main Results:

• The cryo-EM structure revealed an asymmetric IgM-Fc pentamer with a hexagonal, incomplete triangular formation.
• IgM-Fc tailpieces form an amyloid-like structure for pentamer stabilization.
• The J-chain bridges IgM-Fc and pIgR, inducing a significant conformational change in pIgR for complex engagement.

Conclusions:

• The study provides the first structural insights into the IgM-Fc, J-chain, and pIgR complex.
• This structural understanding offers a foundation for deciphering the functional mechanisms of IgM in immune responses.