Acetylcholine receptor-alpha-bungarotoxin interactions: determination of the region-to-region contacts by peptide-peptide interactions and molecular modeling of the receptor cavity.
Acetylcholine receptor-alpha-bungarotoxin interactions: determination of the region-to-region contacts by peptide-peptide interactions and molecular modeling of the receptor cavity.
复制标题
乙酰胆碱受体-α-金环蛇毒素相互作用：通过肽-肽相互作用和受体腔的分子建模确定区域与区域的接触。
DOI：
10.1073/pnas.87.16.6156
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发表时间：
1990
影响因子：
11.1
通讯作者：
Atassi,MZ
中科院分区：
文献类型：
--
作者：
Ruan,KH;Spurlino,J;Quiocho,FA;Atassi,MZ
在本实验室先前的研究中，α-神经毒素对人类和电鳐乙酰胆碱（AcCho）受体（AcChoR）的结合区域以及毒素上受体的结合区域均采用相应分子的合成肽进行了表征。在本工作中，允许代表一个分子的活性区的肽各自与另一个分子的活性区肽中的每一个结合。因此，三种α-银环蛇毒素（α-BTX）合成环肽与代表人AcChoR上毒素结合区域的四种合成肽的相互作用允许测定α-BTX与人受体之间的区域-区域相互作用。基于已知的毒素的三维结构，然后通过计算机建模和能量最小化将受体的活性肽组装到其适当的毒素接触区域。这允许在人AcChoR上三维构建毒素结合腔。空腔看起来是圆锥形的，深度为30.5 A，涉及与α-BTX环区域接触的几个受体区域。参与与α-BTX结合的一个AcCho R区域（在残基125 - 136内）也存在于已知的AcCho结合位点中，因此在三维中证明了参与AcCho活化和α-BTX阻断的关键位点。这种方法的有效性首先建立了三个四肽对应的区域参与结合的α链的人血红蛋白的β链。因此，研究代表两个蛋白质分子的结合区域的肽之间的相互作用可以提供分子识别的方法，通过该方法，如果已知另一个蛋白质的三维结构，则可以描述一个蛋白质上的结合位点。
In previous studies from this laboratory, the binding regions of alpha-neurotoxins on human and Torpedo acetylcholine (AcCho) receptors (AcChoRs) and the binding regions for the receptor on the toxin were characterized with synthetic peptides of the respective molecules. In the present work, peptides representing the active regions of one molecule are each allowed to bind to each of the active-region peptides of the other molecule. Thus, the interaction of three alpha-bungarotoxin (alpha-BTX) synthetic loop peptides with four synthetic peptides representing the toxin-binding regions on human AcChoR permitted the determination of the region-region interactions between alpha-BTX and the human receptor. Based on the known three-dimensional structure of the toxin, the active peptides of the receptor were then assembled to their appropriate toxin-contact regions by computer model building and energy minimization. This allowed the three-dimensional construction of the toxin-binding cavity on human AcChoR. The cavity appears to be conical, 30.5 A in depth, involving several receptor regions that make contact with the alpha-BTX loop regions. One AcChoR region (within residues 125-136) involved in the binding to alpha-BTX also resides in a known AcCho-binding site, thus demonstrating in three dimensions a critical site involved in both AcCho activation and alpha-BTX blocking. The validity of this approach was first established for three of four peptides corresponding to regions on the beta chain of human hemoglobin involved in binding to the alpha chain. Thus, studying the interaction between peptides representing the binding regions of two protein molecules may provide an approach in molecular recognition by which the binding site on one protein can be described if the three-dimensional structure of the other protein is known.