Thyrotropin Receptor Antibody Binding Site Identified
Amino acid residues are crucial for antibody binding
FRIDAY, April 18 (HealthDay News) -- Key amino acid residues in the human thyrotropin receptor (TSHR) are crucial for its binding by a monoclonal antibody, according to the results of a study published online April 3 in Endocrinology.
Chun-Rong Chen, and colleagues from the University of California Los Angeles, investigated the interaction between the murine monoclonal antibody CS-17, which has inverse agonist and antagonist properties, and the TSHR to identify key CS-17 amino acids involved in binding. They note that CS-17 competes for TSH binding to the human but not porcine receptor.
The researchers found that replacing three amino acid residues in the human receptor (Y195, Q235, and S243) with the porcine equivalents totally abolished the ability of CS-17 to bind and reduce cAMP generation without affecting TSH binding. The position of these amino acids in the three-dimensional structure of a related protein suggested that CS-17 and TSH bound to different parts of the receptor.
"In summary, the fortuitous observation that CS-17 binds to the human but not the porcine TSHR had enabled identification of a number of key residues in its epitope," Chen and colleagues conclude.