Sonya Kumar Bharathkar, Benjamin W Parker, Andrey G Malyutin, Nandan Haloi,
Kathryn E Huey-Tubman, Emad Tajkhorshid, and Beth Stadtmueller.
The structures of secretory and dimeric immunoglobulin A.
eLife, 9:e56098, 2020.
(PMC: PMC7707832)
BHAR2020-ET
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.
