Behling R W, Jelinski L W
Squibb Institute for Medical Research, Princeton, NJ 08543.
Biochem Pharmacol. 1990 Jul 1;40(1):49-54. doi: 10.1016/0006-2952(90)90177-m.
NMR data that underscore the importance of the membrane in ligand-receptor interactions were obtained and analyzed. The following hypothesis for acetylcholine (ACh) binding to the acetylcholine receptor (AChR) is proposed: ACh first binds to the membrane, where it adopts its bioactive conformation, and it then rapidly diffuses along the membrane to bind to the AChR in its already-correct conformation. Data used to support this hypothesis include (a) the NMR-determined binding constant of KM = (2.8 +/- 0.6) x 10(3) M-1 for the binding of ACh to the asolectin membrane, (b) the lipid dependence of AChR activity, (c) the location of the ACh binding site close to the membrane surface, and (d) the conformation of ACh in its membrane-bound state. Additional experiments to test this hypothesis are proposed.
获得并分析了强调膜在配体 - 受体相互作用中重要性的核磁共振（NMR）数据。提出了以下关于乙酰胆碱（ACh）与乙酰胆碱受体（AChR）结合的假说：ACh首先与膜结合，在膜上它采用其生物活性构象，然后它沿着膜快速扩散，以与其已处于正确构象的AChR结合。用于支持该假说的数据包括：（a）通过NMR测定的ACh与大豆卵磷脂膜结合的结合常数KM =（2.8±0.6）×10³ M⁻¹；（b）AChR活性对脂质的依赖性；（c）ACh结合位点靠近膜表面的位置；以及（d）ACh在其膜结合状态下的构象。还提出了进一步检验该假说的实验。
