Antibody Fab assembly: the interface residues between CH1 and CL

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• Antibody assembly requires precise light and heavy chain association.
• The interaction between the CH1 domain of the heavy chain and the CL domain of the light chain is crucial for functional antibody structure.
• Understanding these interactions is vital for antibody engineering and therapeutic development.

Purpose of the Study:

• To investigate the conservation of residues at the CH1-CL interface across different antibody classes.
• To identify significant interacting residues within the CH1-CL interface and assess their evolutionary conservation.
• To explore the structural implications of conserved and variable residues, including the role of interface cavities.

Main Methods:

• Analysis of the three-dimensional structures of four antibody fragments (Fabs).
• Examination of residue conservation patterns at the interface between CH1 and CL domains.
• Identification of hydrophobic residues involved in inter-chain contacts within the interface.

Main Results:

• A few hydrophobic residues are buried within the CH1-CL interface, forming numerous contacts and exhibiting high conservation.
• Residues at the periphery of the CH1-CL interface show significant variability.
• A cavity exists within the interface, potentially accommodating changes in central residues while maintaining domain orientation.

Conclusions:

• Highly conserved hydrophobic residues are critical for maintaining the canonical CH1-CL association in antibodies.
• Interface variability at the periphery allows for structural adaptation, while the central cavity may facilitate functional plasticity.
• These findings provide insights into antibody structural stability and evolution.