Immunoglobulin Structure Exhibits Control over CDR Motion

Area of Science:

• Structural biology
• Immunology
• Computational biophysics

Background:

• The immunoglobulin G (IgG) structure's flexibility is critical for its function in antigen binding.
• Understanding internal motions and hinge dynamics is key to elucidating IgG's mechanism of action.

Purpose of the Study:

• To investigate how IgG hinge motions facilitate antigen binding.
• To analyze the influence of protein environment on experimental temperature factors.
• To evaluate the spatial sampling and internal motions of IgG domains.

Main Methods:

• Normal mode analysis (NMA) of an elastic network model (ENM) was employed.
• Analysis focused on identifying hinges, low-frequency modes, and dominant internal motions.
• Protein crystal and packing effects on temperature factors were assessed.

Main Results:

• IgG hinge motions and antigen-binding domains exhibit large spatial sampling, crucial for function.
• Crystallographic temperature factors can be misleading regarding specific functional motions.
• The full IgG structure demonstrates more efficient information transfer than individual F_ab domains.

Conclusions:

• The IgG structure is specifically designed to facilitate antigen binding through large domain excursions.
• Normal mode analysis effectively predicts hinge motions and spatial sampling.
• Coupling of antigen-binding loops with large-scale hinge motions enhances antibody efficacy.