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bioRxiv · 10.1101/2020.09.10.291138

Structure of the Human Secretory Immunoglobulin M Core

Kumar, N.·Arthur, C. P.·Ciferri, C.·Matsumoto, M. L.
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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 highly a conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.

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Kumar, N., Arthur, C. P., Ciferri, C., Matsumoto, M. L.. 2020-09-11. Structure of the Human Secretory Immunoglobulin M Core. https://doi.org/10.1101/2020.09.10.291138

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