TY - JOUR
T1 - The structures of secretory and dimeric immunoglobulin a
AU - Bharathkar, Sonya Kumar
AU - Parker, Benjamin W.
AU - Malyutin, Andrey G.
AU - Haloi, Nandan
AU - Huey-Tubman, Kathryn E.
AU - Tajkhorshid, Emad
AU - Stadtmueller, Beth M.
N1 - Funding Information:
We thank Pamela Bjorkman and members of the Bjorkman lab at Caltech for supporting preliminary work related to this study as well as Jost Vielmetter and the Caltech Protein Expression Center (housed and funded in part by the Caltech Beckman Institute) for guidance on IgA protein expression strategies. We also thank members of the Stadtmueller Laboratory, as well as Emma Slack (ETH Zurich), for insightful conversations regarding the SIgA and dIgA structures. Cryo Electron microscopy was done in the Beckman Institute cryo-EM resource center at Caltech. The STA121 antibody sequence was provided by Luca Piccoli and the Institute for Research in Biomedicine (Bellinzona, Switzerland). This study was funded by University of Illinois Urbana-Champaign start-up funding, National Institutes Health (United States) grant P41-GM10460, and National Institutes Health (United States) grant R01 AI041239. Molecular graphics and analyses performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311. Molecular graphics and analyses performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases.
Publisher Copyright:
© 2020, eLife Sciences Publications Ltd. All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - 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 Igreceptor 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 β-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.
AB - 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 Igreceptor 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 β-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.
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U2 - 10.7554/eLife.56098
DO - 10.7554/eLife.56098
M3 - Article
C2 - 33107820
AN - SCOPUS:85095701705
SN - 2050-084X
VL - 9
SP - 1
EP - 29
JO - eLife
JF - eLife
M1 - e56098
ER -