The structures of secretory IgA in complex with human and bacterial Fc receptors and functional implications for mucosal host-pathogen interactions

Liu, Qianqiao

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https://hdl.handle.net/2142/122205 Copy

Description

Title

The structures of secretory IgA in complex with human and bacterial Fc receptors and functional implications for mucosal host-pathogen interactions

Author(s)

Liu, Qianqiao

Issue Date

2023-10-13

Director of Research (if dissertation) or Advisor (if thesis)

Stadtmueller, Beth

Doctoral Committee Chair(s)

Stadtmueller, Beth

Committee Member(s)

• Nair, Satish
• Huang, Raven
• Wu, Nicholas

Department of Study

Biochemistry

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• IgA
• Streptococcus pyogene
• mucosal immunology
• solid-state NMR
• structural biology.

Abstract

Immunoglobulin (Ig) A serves a dual role as monomeric IgA in the serum and secretory (S) IgA in mucosal secretions. Host IgA Fc receptors (FcαRs), including human FcαR1/CD89, are responsible for mediating IgA's various effector functions. However, pathogens like Streptococcus pyogenes (Group A Streptococcus, GAS), have evolved surface proteins like M4 that can also engage the CD89 binding site on IgA. Despite human mucosa being a reservoir for pathogens, SIgA interactions with CD89 and M4 remain poorly understood. In this dissertation, I investigate the structural and functional aspects of these interactions. Using cryo-EM, I elucidated the structures of M4-SIgA and CD89-SIgA complexes, revealing differing SIgA-binding stoichiometry for M4 and CD89. Results suggest SIgA copies bound to GAS M4 adopt similar orientations on the bacterium's surface, leaving one host FcαR binding site open. Employing fluorescent labeling and confocal microscopy, I successfully visualized SIgA interactions on the GAS cell surface, laying the groundwork for future investigations into host-microbe interactions and bacterial immune evasion mechanisms. These findings highlight previously unrecognized functional consequences of SIgA binding to host and bacterial FcαRs, shedding light on host-microbe co-evolution and IgA's effector functions. In the dissertation's final chapter, I discuss the development of an innovative solid-state NMR pulse sequence for protein structure characterization. This method was successfully applied to a model protein GB1, demonstrating the robustness of this pulse sequence in protein structural determination.

Graduation Semester

2023-12

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/122205

Copyright and License Information

Copyright 2023 Qianqiao Liu

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