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

DOI: 10.1002/2211-5463.13214 DOI Help

Authors: Veronica F. Ilkow (King's College London; Asthma UK Centre in Allergic Mechanisms of Asthma) , Anna M. Davies (King's College London; Asthma UK Centre in Allergic Mechanisms of Asthma) , Balvinder Dhaliwal (King's College London; Asthma UK Centre in Allergic Mechanisms of Asthma) , Andrew J. Beavil (King's College London; Asthma UK Centre in Allergic Mechanisms of Asthma) , Brian J. Sutton (King's College London; Asthma UK Centre in Allergic Mechanisms of Asthma) , James M. Mcdonnell (King's College London; Asthma UK Centre in Allergic Mechanisms of Asthma)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Open Bio

State: Published (Approved)
Published: June 2021
Diamond Proposal Number(s): 9495

Open Access Open Access

Abstract: Immunoglobulin E (IgE) is a central regulatory and triggering molecule of allergic immune responses.IgE’s interaction with CD23 modulates both IgE production and functional activities.CD23 is a non-canonical immunoglobulin receptor, unrelated to receptors of other antibody isotypes. Human CD23 is a calcium-dependent (C-type) lectin-like domain that has apparently lost its carbohydrate binding capability. The calcium binding site classically required for carbohydrate binding in C-type lectins is absent in human CD23 but is present in the murine molecule.To determine if the absence of this calcium binding site affects the structure and function of human CD23, CD23 mutant proteins with increasingly ‘murine-like’ sequences were generated. Restoration of the calcium binding site was confirmed by NMR spectroscopy and structures of mutant human CD23 proteins were determined by X-ray crystallography, although no electron density for calcium was observed.This study offers insights into the evolutionary differences between murine and human CD23, and some of the functional differences between CD23 in different species.

Journal Keywords: IgE; Immunoglobulin E; CD23; FcεRII; CTLD; calcium

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 03/06/2021 10:05

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Non-Communicable Diseases Structural biology Allergic Diseases

Technical Tags:

Diffraction Macromolecular Crystallography (MX)