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.
- Sonya Kumar Bharathkar
- Benjamin W Parker
- Beth Stadtmueller
- Beth Stadtmueller
- Nandan Haloi
- Emad Tajkhorshid
- 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.
- Sjors HW Scheres, MRC Laboratory of Molecular Biology, United Kingdom
- Received: February 17, 2020
- Accepted: October 26, 2020
- Accepted Manuscript published: October 27, 2020 (version 1)
© 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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