Mimura C S, Holbrook S R, Ames G F
Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):84-8. doi: 10.1073/pnas.88.1.84.
The amino acid sequences of 17 bacterial membrane proteins that are components of periplasmic permeases and function in the uptake of a variety of small molecules and ions are highly homologous to each other and contain sequence motifs characteristic of nucleotide-binding proteins. These proteins are known to bind ATP and are postulated to be the energy-coupling components of the permeases. Several medically important eukaryotic proteins, including the multidrug-resistance transporters and the protein encoded by the cystic fibrosis gene, are also homologous to this family. By multiple sequence alignment of these 17 proteins, the consensus sequence, secondary structure, and surface exposure were predicted. The secondary structural motifs that are conserved among nucleotide-binding proteins were identified in adenylate kinase, p21ras, and elongation factor Tu by superposition of their known tertiary structures. The equivalent secondary structural elements in the predicted conserved component were located. These, together with sequence information, served as guides for alignment with adenylate kinase. A model for the structure of the ATP-binding domain of the permease proteins is proposed by analogy to the adenylate kinase structure. The characteristics of several permease mutations and biochemical data lend support to the model.
17种细菌膜蛋白的氨基酸序列彼此高度同源，这些膜蛋白是周质通透酶的组成部分，在多种小分子和离子的摄取中发挥作用，并且包含核苷酸结合蛋白的特征性序列基序。已知这些蛋白能结合ATP，并被推测为通透酶的能量偶联成分。几种医学上重要的真核蛋白，包括多药耐药转运蛋白和囊性纤维化基因编码的蛋白，也与这个家族同源。通过对这17种蛋白进行多序列比对，预测了共有序列、二级结构和表面暴露情况。通过叠加腺苷酸激酶、p21ras和延伸因子Tu的已知三级结构，在其中鉴定出了核苷酸结合蛋白中保守的二级结构基序。确定了预测保守成分中的等效二级结构元件。这些元件与序列信息一起，作为与腺苷酸激酶比对的指导。通过类比腺苷酸激酶结构，提出了通透酶蛋白ATP结合结构域的结构模型。几种通透酶突变的特征和生化数据支持了该模型。
