The TSHR A-subunit monomer cannot represent both forms (active and inactive) of purified A-subunits.

The crystal structure of a Fab for human monoclonal TSAb M22 (red) in complex with the major component of TSHR A-subunit (amino acids 22–260; green) has been solved (6) (protein data base 3GO4), as has the crystal structure of a Fab for mouse monoclonal antibody (mAb) 3BD10 (blue/violet) generated to the human A-subunit (7) (protein data base 4QT5). TSAb M22 specifically recognizes the active, not the inactive, A-subunit form (8, 9). Conversely, mAb 3BD10 only recognizes inactive A-subunits (5). Guided by amino acids contributing to its epitope, the 3BD10 Fab can be docked in silico with the M22/TSHR structure (7). Because both M22 and 3BD10 can simultaneously bind to the TSHR A-subunit monomer, the latter cannot explain the reciprocally exclusive TSAb and 3BD10 binding that is observed experimentally (5).