Tams J W, Knudsen S M, Fahrenkrug J
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Denmark.
Recept Channels. 1998;5(2):79-90.
An arrangement of the seven transmembrane alpha-helices of the G protein-coupled Secretin receptor family is proposed. The helices of 27 homologous receptor sequences were plotted as helical wheels. The solvent inaccessible portion of each helix was used to assign relative orientations. They were arranged according to two criteria: 1) conserved, hydrophilic residues and aligned positions with restricted volume changes face the other helices and 2) aligned positions with low identity and large volume change face the lipid. The positive inside rule confirms the assumption that loops connecting transmembrane helices I-II, III-IV, V-VI and the C-terminal part of the receptors are intracellular. Our model approach was tested using the Bacteriorhodopsin family. The use of volume changes at each position in the transmembrane helix was crucial for the good correlation of the orientation of the helices using the model approach and the structure of bacteriorhodopsin solved by electron microscopy [Grigorieff N, Ceska TA, Downing KH, Baldwin JM, and Henderson R (1996) J Mol Biol 259 393-421]. The tests of our modelling approach showed that six helices were within a 15 degrees derivation in the orientation and five helices were within a horizontal derivation of two residues. The largest orientational derivations of a helix were 40 degrees and the largest horizontal displacement was four residues. A long stretch of side chains predicted to possess low resistance to movement in helix V of the Secretin receptor family suggests an involvement in receptor activation. Comparison of the Secretin receptor family and the larger G protein-coupled Rhodopsin family showed many similarities, despite the lack of obvious sequence identity.
本文提出了G蛋白偶联促胰液素受体家族七个跨膜α螺旋的排列方式。将27个同源受体序列的螺旋绘制成螺旋轮。每个螺旋的溶剂不可及部分用于确定相对方向。它们根据两个标准进行排列：1）保守的亲水性残基和体积变化受限的对齐位置面向其他螺旋；2）低同源性和大体积变化的对齐位置面向脂质。“正内规则”证实了跨膜螺旋I-II、III-IV、V-VI以及受体C端部分之间的环是细胞内的这一假设。我们使用细菌视紫红质家族对模型方法进行了测试。跨膜螺旋中每个位置的体积变化对于使用模型方法确定螺旋方向与通过电子显微镜解析的细菌视紫红质结构之间的良好相关性至关重要[Grigorieff N, Ceska TA, Downing KH, Baldwin JM, and Henderson R (1996) J Mol Biol 259 393 - 421]。我们建模方法的测试表明，六个螺旋在方向上的偏差在15度以内，五个螺旋在水平方向上的偏差在两个残基以内。一个螺旋的最大方向偏差为40度，最大水平位移为四个残基。促胰液素受体家族螺旋V中预计对运动具有低抗性的一长段侧链表明其参与受体激活。尽管缺乏明显的序列同源性，但促胰液素受体家族与更大的G蛋白偶联视紫红质家族的比较显示出许多相似之处。
