3-DIMENSIONAL LOCATION OF THE MAIN IMMUNOGENIC REGION OF THE ACETYLCHOLINE-RECEPTOR

About two-thirds of the antibodies to the nicotinic acetylcholine (ACh ) receptor in patients with the autoimmune disease myasthenia gravis b ind to the main immunogenic region (MIR). This is a small, well-define d region on each of the two alpha subunits, containing residues 67-76 (alpha 67-76). By determining the structure of the ACh receptor comple xed with two different fragments of an MIR-directed antibody, we have determined the three-dimensional location of the MIR (and therefore re sidues alpha 67-76) to be at the extreme synaptic end of each alpha su bunit. The antibody fragments extend from the binding site away from t he receptor axis and into the synaptic cleft, minimizing any steric in terference neighboring ACh receptors might have with their binding.