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Published March 4, 2016 | Published + Supplemental Material
Journal Article Open

The structure and dynamics of secretory component and its interactions with polymeric immunoglobulins


As a first-line vertebrate immune defense, the polymeric immunoglobulin receptor (pIgR) transports polymeric IgA and IgM across epithelia to mucosal secretions, where the cleaved ectodomain (secretory component; SC) becomes a component of secretory antibodies, or when unliganded, binds and excludes bacteria. Here we report the 2.6Å crystal structure of unliganded human SC (hSC) and comparisons with a 1.7Å structure of teleost fish SC (tSC), an early pIgR ancestor. The hSC structure comprises five immunoglobulin-like domains (D1-D5) arranged as a triangle, with an interface between ligand-binding domains D1 and D5. Electron paramagnetic resonance measurements confirmed the D1-D5 interface in solution and revealed that it breaks upon ligand binding. Together with binding studies of mutant and chimeric SCs, which revealed domain contributions to secretory antibody formation, these results provide detailed models for SC structure, address pIgR evolution, and demonstrate that SC uses multiple conformations to protect mammals from pathogens.

Additional Information

© 2015 Stadtmueller et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 06 August 2015; Accepted: 21 January 2016; Published: 04 March 2016. We thank Jost Vielmetter and the Caltech Protein Expression Center for assistance with protein expression, and Jens Kaiser, Pavle Nikolovski and the Caltech Molecular Observatory (supported by the Gordon and Betty Moore Foundation) for crystallography support. We also thank members of the Bjorkman and Hubbell labs for insightful discussions, and Collin Kieffer and Anthony West for critical comments on the manuscript. Funders: National Institute of Allergy and Infectious Diseases (AI04123); Cancer Research Institute Irving Postdoctoral Fellowship; The Jules Stein Professorship Endowment; National Institutes of Health EY005216. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author contributions: BMS, CJL, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article; KEHT, Acquisition of data, Drafting or revising the article; ZY, Acquisition of data, Analysis and interpretation of data; WLH, Analysis and interpretation of data, Drafting or revising the article; PJB, Conception and design, Analysis and interpretation of data, Drafting or revising the article. Accession numbers: Crystallographic atomic coordinates and structure factors have been deposited in the Protein Data Bank (http://www.rcsb.org) with codes 5D4K (hSC) and 5F1S (tSC).

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