Torres Allan M, Alewood Dianne, Alewood Paul F, Gallagher Clifford H, Kuchel Philip W
Department of Biochemistry, University of Sydney, Sydney, NSW 2006, Australia.
Toxicon. 2002 Jun;40(6):711-9. doi: 10.1016/s0041-0101(01)00266-5.
Nuclear magnetic resonance spectroscopy was used to investigate the conformations of the platypus venom C-type natriuretic peptide A (OvCNPa) in aqueous solutions and in solutions containing sodium dodecyl sulfate (SDS) micelles. The chemically synthesized OvCNPa showed a substantial decrease in flexibility in aqueous solution at 10 degrees C, allowing the observation of medium- and long-range nuclear Overhauser enhancement (NOE) connectivities. Three-dimensional structures calculated using these data showed flexible and reasonably well-defined regions, the locations of which were similar in the two solvents. In aqueous solution, the linear part that spans residues 3-14 was basically an extended conformation while the cyclic portion, defined by residues 23-39, contained a series of beta-turns. The overall shape of the cyclic portion was similar to that observed for an atrial natriuretic peptide (ANP) variant in aqueous solution. OvCNPa adopted a different conformation in SDS micelles wherein the N-terminal region, defined by residues 2-10, was more compact, characterised by turns and a helix, while the cyclic region had turns and an overall shape that was fundamentally different from those structures observed in aqueous solution. The hydrophobic cluster, situated at the centre of the ring of the structure in aqueous solution, was absent in the structure in the presence of SDS micelles. Thus, OvCNPa interacts with SDS micelles and can possibly form ion-channels in cell membranes.
利用核磁共振光谱研究了鸭嘴兽毒液C型利钠肽A（OvCNPa）在水溶液和含有十二烷基硫酸钠（SDS）胶束的溶液中的构象。化学合成的OvCNPa在10℃的水溶液中灵活性大幅降低，使得能够观察到中远程核Overhauser效应（NOE）连接。利用这些数据计算出的三维结构显示出灵活且定义合理的区域，其位置在两种溶剂中相似。在水溶液中，跨越3 - 14位残基的线性部分基本呈伸展构象，而由23 - 39位残基定义的环状部分包含一系列β - 转角。环状部分的整体形状与在水溶液中观察到的心房利钠肽（ANP）变体相似。OvCNPa在SDS胶束中采用了不同的构象，其中由2 - 10位残基定义的N端区域更紧凑，其特征为转角和一个螺旋，而环状区域有转角且整体形状与在水溶液中观察到的结构有根本不同。位于水溶液中结构环中心的疏水簇在存在SDS胶束的结构中不存在。因此，OvCNPa与SDS胶束相互作用，并可能在细胞膜中形成离子通道。
