Human immunoglobulin E flexes between acutely bent and extended conformations.

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• Previous crystallographic and solution studies indicated that immunoglobulin E (IgE) molecules are predominantly bent in their Fc region.
• Crystal structures revealed the Cɛ2 domain pair folded back onto the Cɛ3-Cɛ4 domains, suggesting a fixed bent conformation.

Purpose of the Study:

• To investigate whether IgE molecules can adopt extended conformations beyond the previously observed bent states.
• To explore the conformational flexibility of the IgE-Fc region in solution.

Main Methods:

• X-ray crystallography to determine the structure of IgE-Fc in an extended conformation.
• Molecular dynamics simulations to analyze conformational dynamics.
• Calorimetry, stopped-flow kinetics, surface plasmon resonance (SPR), and Förster resonance energy transfer (FRET) to study IgE-Fc behavior in solution.

Main Results:

• The crystal structure of IgE-Fc was determined in a fully extended, symmetrical conformation.
• Solution studies confirmed that IgE-Fc can indeed adopt extended conformations.
• Demonstrated significant conformational flexibility in the IgE-Fc region.

Conclusions:

• IgE-Fc is not exclusively bent but can exist in diverse conformational states, including extended forms.
• This conformational plasticity provides new insights into IgE function in allergen binding and B-cell receptor activity.
• Understanding IgE conformational diversity is crucial for developing targeted therapies for allergic diseases.