Three-dimensional structure of an intact human immunoglobulin

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• Human IgG1 antibodies are crucial for immune responses.
• Understanding IgG1 structure is key to antibody function.
• Previous studies focused on immunoglobulin fragments.

Purpose of the Study:

• To determine the low-resolution structure of a complete human IgG1.
• To elucidate the role of the carbohydrate moiety in IgG1 structure.
• To investigate the flexibility of the Fab region.

Main Methods:

• Utilized known domain coordinates from crystallographic studies.
• Modeled the complete human IgG1 structure.
• Analyzed inter-domain and inter-region contacts.

Main Results:

• The Fc portion mirrors isolated Fc fragment structures.
• The carbohydrate moiety is central to CH2 domain interaction.
• Carbohydrate significantly interfaces with Fc and Fab regions.
• Fab regions exhibit intermediate orientations, highlighting switch region flexibility.

Conclusions:

• The determined IgG1 structure provides insights into antibody conformation.
• The carbohydrate moiety is critical for Fc region integrity and function.
• Data do not support a two-state allosteric model for antibody effector functions.