Reviving lost binding sites: Exploring calcium-binding site transitions between human and murine CD23

Veronica F Ilkow1,2, Anna M Davies1,2, Balvinder Dhaliwal1,2

  • 1Randall Centre for Cell & Molecular Biophysics, King's College London, UK.

FEBS Open Bio
|June 2, 2021
PubMed

Insights

This study explores how human CD23, a key molecule in allergic responses, differs from its mouse counterpart. Researchers investigated structural and functional changes related to a missing calcium-binding site in human CD23.

Area of Science:

  • Immunology
  • Structural Biology
  • Evolutionary Biology

Background:

  • Immunoglobulin E (IgE) plays a critical role in allergic immune responses.
  • CD23 is an IgE receptor that regulates IgE production and function.
  • Human CD23, unlike murine CD23, lacks a functional calcium-binding site in its C-type lectin domain.

Purpose of the Study:

  • To investigate the structural and functional consequences of the absent calcium-binding site in human CD23.
  • To compare human and murine CD23 through the creation of mutant proteins with increasing "murine-like" sequences.
  • To understand evolutionary differences in CD23 structure and function.

Main Methods:

  • Generation of CD23 mutant proteins with progressively murine-like sequences.
  • Nuclear Magnetic Resonance (NMR) spectroscopy to confirm restoration of the calcium-binding site.
  • X-ray crystallography to determine the structures of mutant human CD23 proteins.

Main Results:

  • Mutant human CD23 proteins were generated, incorporating features of murine CD23.
  • NMR confirmed the presence of the calcium-binding site in engineered mutants.
  • X-ray crystallography provided structural insights, though calcium binding was not directly observed.

Conclusions:

  • The study elucidates evolutionary divergence between human and murine CD23.
  • Structural and functional differences in CD23 across species are highlighted.
  • Insights into the role of the calcium-binding site in CD23 structure and function are provided.

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