Structure of the human secretory immunoglobulin M core

Structure. 2021 Jun 3;29(6):564-571.e3. doi: 10.1016/j.str.2021.01.002. Epub 2021 Jan 28.

Abstract

Immunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) and the secretory component (SC) of pIgR, secretory IgA and IgM (sIgA and sIgM) play critical roles in host-pathogen defense. Recently, we determined the structure of sIgA-Fc which elucidated the mechanism of polymeric IgA assembly and revealed an extensive binding interface between IgA-Fc, JC, and SC. Despite low sequence identity shared with IgA-Fc, IgM-Fc also undergoes JC-mediated assembly and binds pIgR. Here, we report the structure of sIgM-Fc and carryout a systematic comparison to sIgA-Fc. Our structural analysis reveals a remarkably conserved mechanism of JC-templated oligomerization and SC recognition of both IgM and IgA through a highly conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.

Keywords: cryo-electron microscopy; immunoglobulin; mucosa; transcytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Immunoglobulin A, Secretory / chemistry*
  • Immunoglobulin A, Secretory / metabolism
  • Immunoglobulin J-Chains / metabolism*
  • Immunoglobulin M / chemistry*
  • Immunoglobulin M / metabolism
  • Models, Molecular
  • Protein Conformation
  • Secretory Component / metabolism*
  • Structural Homology, Protein
  • Transcytosis

Substances

  • Immunoglobulin A, Secretory
  • Immunoglobulin J-Chains
  • Immunoglobulin M
  • Secretory Component
  • secretory IgM