Wisnieski B J, Bramhall J S
Nature. 1981 Jan 22;289(5795):319-21. doi: 10.1038/289319a0.
There has been much speculation about the mechanism by which cholera toxin exerts its effect on the cytoplasmic side of the membranes with which it interacts. After the pentamer of B subunits (5B) binds to membrane receptors, particularly the monosialylganglioside GM1, the disulphide-linked dimer A1SSA2 (which together with 5B constitutes the complete toxin) is thought to penetrate the membrane, perhaps through a channel formed by 5B and become reduced so that A1SH units reach the cytoplasm and stimulate adenylate cyclase. Evidence for this mechanism is circumstantial. If it is correct, a compound which will specifically label intramembranous sections of the toxin should label the channel-forming B subunits but not the channel-contained A1 subunit. We have tested this prediction with a photoreactive glycolipid compound and have obtained the opposite result. Therefore, we propose that only the A1 subunit enters the membrane and we provide here data on the kinetics of that process.
关于霍乱毒素对其相互作用的细胞膜胞质侧发挥作用的机制，一直存在诸多推测。在B亚基五聚体（5B）与膜受体结合后，特别是与单唾液酸神经节苷脂GM1结合后，二硫键连接的二聚体A1SSA2（它与5B一起构成完整毒素）被认为会穿透细胞膜，可能是通过5B形成的通道，并被还原，从而使A1SH单元到达细胞质并刺激腺苷酸环化酶。支持这一机制的证据是间接的。如果这一机制正确，那么一种能特异性标记毒素膜内部分的化合物应该标记形成通道的B亚基，而不是包含在通道内的A1亚基。我们用一种光反应性糖脂化合物对这一预测进行了测试，却得到了相反的结果。因此，我们提出只有A1亚基进入细胞膜，并在此提供该过程动力学的数据。
