Structure and specificity of antibody molecules.

Area of Science:

• Structural Biology
• Immunology
• Biochemistry

Background:

• Antibodies are key to the immune system, recognizing specific antigens.
• Understanding antibody structure is vital for elucidating their function and developing therapeutics.
• The Fab' fragment represents the antigen-binding portion of an antibody.

Purpose of the Study:

• To determine the high-resolution three-dimensional structure of the Fab' fragment of a human myeloma protein (IgG1 (lambda) New).
• To analyze the structural basis of the antibody's active site, particularly the role of hypervariable regions.
• To investigate the binding of ligands to the antibody's active site.

Main Methods:

• X-ray crystallographic analysis to a resolution of 0.2 nm.
• Determination of the three-dimensional model of the Fab' New fragment.
• Investigation of crystalline ligand-Fab' New complexes using difference Fourier maps.

Main Results:

• The structure reveals that both variable and constant homology regions contain two irregular beta-sheets surrounding a hydrophobic core.
• Hypervariable regions of the light and heavy chains are spatially proximate, defining the active site.
• Analysis of ligand-Fab' New complexes provides insights into binding interactions.

Conclusions:

• The determined structure provides a detailed model for understanding antibody active site formation and function.
• The spatial arrangement of hypervariable regions is critical for antibody specificity.
• This structural information aids in understanding the biological function and specificity of antibodies.