Dwyer D S
Department of Psychiatry, University of Alabama, Birmingham 35294.
Life Sci. 1989;45(5):421-9. doi: 10.1016/0024-3205(89)90628-0.
Mice were immunized with alpha-bungarotoxin (BGT), a nearly irreversible antagonist of the acetylcholine receptor (AChR), to produce monoclonal antibodies (Mabs). One of the Mabs (JMC2.7) bound not only to BGT, but to the AChR as well. To understand the molecular basis for this novel cross-reaction, the amino acid sequences of these proteins were searched for areas of similarity which might constitute the shared epitope. A number of short segments of sequence homology were found, one of them representing the BGT-binding site of the AChR. Because a portion of BGT resembles that part of the AChR that binds toxin, the self-binding of BGT was evaluated. As shown here, BGT binds specifically to itself to form dimers. In order to extend these observations, other ligand-receptor pairs were examined for sequence homology. The sodium channel and alpha-scorpion toxins were found to have distinct areas of similarity, as do interleukin 2 (IL-2) and the IL-2 receptor. As a general principle, we propose that peptide ligands and their receptors may often share amino acid sequence homology. In fact, the sites of interaction between two proteins may largely be determined by these regions of similarity.
用α-银环蛇毒素（BGT）对小鼠进行免疫，BGT是一种几乎不可逆的乙酰胆碱受体（AChR）拮抗剂，以产生单克隆抗体（Mab）。其中一种单克隆抗体（JMC2.7）不仅能与BGT结合，还能与AChR结合。为了理解这种新型交叉反应的分子基础，对这些蛋白质的氨基酸序列进行搜索，寻找可能构成共同表位的相似区域。发现了许多短的序列同源片段，其中一个代表AChR的BGT结合位点。由于BGT的一部分类似于AChR中结合毒素的部分，因此对BGT的自身结合进行了评估。如下所示，BGT特异性地与自身结合形成二聚体。为了扩展这些观察结果，对其他配体-受体对进行了序列同源性检测。发现钠通道和α-蝎毒素有不同的相似区域，白细胞介素2（IL-2）和IL-2受体也是如此。作为一个普遍原则，我们提出肽配体及其受体可能经常共享氨基酸序列同源性。事实上，两种蛋白质之间的相互作用位点可能很大程度上由这些相似区域决定。
