Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-0032, Japan.
J Am Chem Soc. 2011 Aug 31;133(34):13571-6. doi: 10.1021/ja204451g. Epub 2011 Aug 5.
Bacteriophage T4 penetrates the outer membrane of Escherichia coli using a multifunctional device composed of a gene product 5 (gp5) protein trimer. We report that gp5 sequentially exerts distinct functions along the course of penetration stages induced by screw motion. A triple-stranded β-helix of gp5 acts as a cell-puncturing drill bit to make a hole on the membrane and then send the lipids upward efficiently by strong charge interactions. The gp5 lysozyme domains, which degrade the peptidoglycan layer later, are shown to play novel roles to enlarge the hole and control the release of the β-helix. The lysozyme active site is protected from lipid binding during the penetration and is exposed after the β-helix release. Intrinsic multiple functions of gp5 are shown to be served in turn regulated by gradual change of interdomain interactions, which enables the initial infection process with single protein trimer by continuous screw motion. The results of lysozyme domain should be understood as the case where a single-function protein acquired multiple chemical functions through interplay with other domains in a multidomain protein.
噬菌体 T4 使用由基因产物 5（gp5）蛋白三聚体组成的多功能设备穿透大肠杆菌的外膜。我们报告说，gp5 沿着由螺旋运动诱导的穿透阶段的顺序发挥不同的功能。gp5 的三股β-螺旋充当细胞穿孔钻头，在膜上打孔，然后通过强烈的电荷相互作用有效地将脂质向上输送。后来降解肽聚糖层的 gp5 溶菌酶结构域被证明具有扩大孔和控制β-螺旋释放的新作用。溶菌酶活性位点在穿透过程中受到脂质结合的保护，在β-螺旋释放后暴露。gp5 的内在多重功能依次被证明受到结构域间相互作用的逐渐变化的调节，这使得通过连续的螺旋运动用单个蛋白三聚体进行初始感染过程成为可能。溶菌酶结构域的结果应该被理解为单个功能蛋白通过与多域蛋白中的其他结构域相互作用获得多个化学功能的情况。
