Beroukhim R, Unwin N
Medical Research Council, Laboratory of Molecular Biology, Cambridge, England.
Neuron. 1995 Aug;15(2):323-31. doi: 10.1016/0896-6273(95)90037-3.
About two-thirds of the antibodies to the nicotinic acetylcholine (ACh) receptor in patients with the autoimmune disease myasthenia gravis bind to the main immunogenic region (MIR). This is small, well-defined region on each of the two alpha subunits, containing residues 67-76 (alpha 67-76). By determining the structure of the ACh receptor complexed with two different fragments of an MIR-directed antibody, we have determined the three-dimensional location of the MIR (and therefore residues alpha 67-76) to be at the extreme synaptic end of each alpha subunit. The antibody fragments extend from the binding site away from the receptor axis and into the synaptic cleft, minimizing any steric interference neighboring ACh receptors might have with their binding.
在自身免疫性疾病重症肌无力患者中，约三分之二的抗烟碱型乙酰胆碱（ACh）受体抗体与主要免疫原性区域（MIR）结合。该区域位于两个α亚基各自上一个小的、界限明确的区域，包含第67 - 76位残基（α67 - 76）。通过确定与MIR导向抗体的两个不同片段复合的ACh受体的结构，我们已确定MIR（以及α67 - 76残基）在每个α亚基的极端突触末端的三维位置。抗体片段从结合位点延伸，远离受体轴并进入突触间隙，将相邻ACh受体可能对其结合产生的任何空间干扰降至最低。
