1. Immunology and Inflammation
  2. Structural Biology and Molecular Biophysics
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The structures of Secretory and dimeric Immunoglobulin A

  1. Sonya Kumar Bharathkar
  2. Benjamin W Parker
  3. Andrey G Malyutin
  4. Nandan Haloi
  5. Kathryn E Huey-Tubman
  6. Emad Tajkhorshid
  7. Beth Stadtmueller  Is a corresponding author
  1. University of Illinois-Urbana Champaign, United States
  2. California Institute of Technology, United States
Research Article
  • Cited 2
  • Views 1,155
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Cite this article as: eLife 2020;9:e56098 doi: 10.7554/eLife.56098

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).

The following data sets were generated

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Author details

  1. Sonya Kumar Bharathkar

    Department of Biochemistry, University of Illinois-Urbana Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Benjamin W Parker

    Department of Biochemistry, University of Illinois-Urbana Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Andrey G Malyutin

    Division of Biology and Biological Engineering; Beckman Institute, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Nandan Haloi

    Department of Biochemistry; Center for Biophysics and Quantitative Biology, University of Illinois-Urbana Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Kathryn E Huey-Tubman

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Emad Tajkhorshid

    Biochemistry, University of Illinois-Urbana Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8434-1010

  7. Beth Stadtmueller

    Department of Biochemistry, University of Illinois-Urbana Champaign, Urbana, United States
    For correspondence
    bethms@illinois.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0637-3206

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.

Reviewing Editor

  1. Sjors HW Scheres, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: February 17, 2020
  2. Accepted: October 26, 2020
  3. Accepted Manuscript published: October 27, 2020 (version 1)
  4. Version of Record published: December 1, 2020 (version 2)

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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