Eriksson Hanna M, Wessman Per, Ge Changrong, Edwards Katarina, Wieslander Ake
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden.
J Biol Chem. 2009 Dec 4;284(49):33904-14. doi: 10.1074/jbc.M109.021618. Epub 2009 Sep 18.
The morphology and curvature of biological bilayers are determined by the packing shapes and interactions of their participant molecules. Bacteria, except photosynthetic groups, usually lack intracellular membrane organelles. Strong overexpression in Escherichia coli of a foreign monotopic glycosyltransferase (named monoglycosyldiacylglycerol synthase), synthesizing a nonbilayer-prone glucolipid, induced massive formation of membrane vesicles in the cytoplasm. Vesicle assemblies were visualized in cytoplasmic zones by fluorescence microscopy. These have a very low buoyant density, substantially different from inner membranes, with a lipid content of > or = 60% (w/w). Cryo-transmission electron microscopy revealed cells to be filled with membrane vesicles of various sizes and shapes, which when released were mostly spherical (diameter approximately 100 nm). The protein repertoire was similar in vesicle and inner membranes and dominated by the glycosyltransferase. Membrane polar lipid composition was similar too, including the foreign glucolipid. A related glycosyltransferase and an inactive monoglycosyldiacylglycerol synthase mutant also yielded membrane vesicles, but without glucolipid synthesis, strongly indicating that vesiculation is induced by the protein itself. The high capacity for membrane vesicle formation seems inherent in the glycosyltransferase structure, and it depends on the following: (i) lateral expansion of the inner monolayer by interface binding of many molecules; (ii) membrane expansion through stimulation of phospholipid synthesis, by electrostatic binding and sequestration of anionic lipids; (iii) bilayer bending by the packing shape of excess nonbilayer-prone phospholipid or glucolipid; and (iv) potentially also the shape or penetration profile of the glycosyltransferase binding surface. These features seem to apply to several other proteins able to achieve an analogous membrane expansion.
生物双层膜的形态和曲率由其参与分子的堆积形状和相互作用决定。除光合菌群外,细菌通常缺乏细胞内膜细胞器。在大肠杆菌中强烈过表达一种外源单拓扑糖基转移酶(称为单糖基二酰甘油合酶),该酶合成一种不易形成双层膜的糖脂,可诱导细胞质中大量形成膜泡。通过荧光显微镜在细胞质区域观察到了膜泡聚集体。这些膜泡的浮力密度非常低,与内膜有很大不同,脂质含量≥60%(w/w)。冷冻透射电子显微镜显示细胞内充满了各种大小和形状的膜泡,释放后大多为球形(直径约100nm)。膜泡和内膜中的蛋白质组成相似,且以糖基转移酶为主。膜极性脂质组成也相似,包括外源糖脂。一种相关的糖基转移酶和一个无活性的单糖基二酰甘油合酶突变体也产生了膜泡,但没有糖脂合成,这有力地表明膜泡化是由该蛋白质本身诱导的。膜泡形成的高能力似乎是糖基转移酶结构所固有的,并且取决于以下几点:(i)许多分子通过界面结合使内膜单层横向扩张;(ii)通过静电结合和隔离阴离子脂质刺激磷脂合成来实现膜扩张;(iii)过量不易形成双层膜的磷脂或糖脂的堆积形状导致双层膜弯曲;(iv)可能还取决于糖基转移酶结合表面的形状或穿透情况。这些特征似乎也适用于其他几种能够实现类似膜扩张的蛋白质。