The structures of Secretory and dimeric Immunoglobulin A
- University of Illinois-Urbana Champaign, United States
- California Institute of Technology, United States
Abstract
Secretory (S) Immunoglobulin (I) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a b-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen binding fragments (Fabs) and preserves steric accessibility to receptor binding sites, likely influencing antigen binding and effector functions.
Data availability
SIgA and dIgA cryoEM maps and structure coordinate files have been deposited in the EM databank with accession codes EMD-22309 (dIgA) and EMD-22310 (SIgA) and the protein databank with accession codes 7JG1(dIgA) and 7JG2 (SIgA).
Article and author information
Author details
Funding
University of Illinois at Urbana-Champaign (Start-up funding)
- Sonya Kumar Bharathkar
University of Illinois at Urbana-Champaign (Start-up funding)
- Benjamin W Parker
University of Illinois at Urbana-Champaign (Start-up funding)
- Beth Stadtmueller
National Institute of Allergy and Infectious Diseases (AI04123)
- Beth Stadtmueller
National Institute of General Medical Sciences (P41-GM10460)
- Nandan Haloi
National Institute of General Medical Sciences (P41-GM10460)
- Emad Tajkhorshid
National Institute of Allergy and Infectious Diseases (AI04123)
- Kathryn E Huey-Tubman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Kumar Bharathkar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The structures of Secretory and dimeric Immunoglobulin A
eLife 9:e56098.
https://doi.org/10.7554/eLife.56098
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