UbiG和Coq3(真核生物中的直向同源物)是SAM-MTases(S-腺苷甲硫氨酸依赖性甲基转移酶),其催化从原核生物到真核生物的CoQ生物合成中的两个O-甲基化步骤。然而,它们发挥作用的详细分子机制仍然难以捉摸。在本论文中,我们报道UbiG/Coq3定义了一类新的膜结合蛋白。大肠杆菌UbiG与含有PG(磷脂酰甘油)或CL(心磷脂,或二磷脂酰甘油),大肠杆菌质膜的两种主要脂质成分,而人类和酵母Coq3对富含CL的脂质体表现出强烈的偏好,线粒体膜的特征脂质。来自大肠杆菌的UbiG的晶体结构以2.1µ(1µ=0.1nm)分辨率确定。该结构表现出典型的I类SAM-MTase折叠,有几种变化,包括链β5和螺旋α10之间的独特插入。这种插入是高度保守的并且是膜结合所必需的。关键残基的突变使得UbiG不能在体外有效结合脂质体,并且突变体不能在体内挽救ΔubiG菌株的表型。一起来看,我们的结果揭示了UbiG/Coq3蛋白的新生化功能。
UbiG and Coq3 (orthologue in eukaryotes) are SAM-MTases (S-adenosylmethionine-dependent methyltransferases) that catalyse both O-methylation steps in CoQ biosynthesis from prokaryotes to eukaryotes. However, the detailed molecular mechanism by which they function remains elusive. In the present paper, we report that UbiG/Coq3 defines a novel class of membrane-binding proteins. Escherichia coli UbiG binds specifically to liposomes containing PG (phosphatidylglycerol) or CL (cardiolipin, or diphosphatidylglycerol), two major lipid components of the E. coli plasma membrane, whereas human and yeast Coq3 display a strong preference for liposomes enriched with CL, a signature lipid of the mitochondrial membrane. The crystal structure of UbiG from E. coli was determined at 2.1 Å (1 Å = 0.1 nm) resolution. The structure exhibits a typical Class I SAM-MTase fold with several variations, including a unique insertion between strand β5 and helix α10. This insertion is highly conserved and is required for membrane binding. Mutation of the key residues renders UbiG unable to efficiently bind liposome in vitro and the mutant fails to rescue the phenotype of ΔubiG strain in vivo. Taken together, our results shed light on a novel biochemical function of the UbiG/Coq3 protein.