Structural and biochemical studies reveal UbiG/Coq3 as a class of novel membrane-binding proteins.
Structural and biochemical studies reveal UbiG/Coq3 as a class of novel membrane-binding proteins.
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DOI：
10.1042/bj20150329
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Yuwei Zhu;Bo Wu;Xu Zhang;Xiaojiao Fan;L. Niu;Xu Li;Junfeng Wang;M. Teng
中科院分区：
文献类型：
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作者：
Yuwei Zhu;Bo Wu;Xu Zhang;Xiaojiao Fan;L. Niu;Xu Li;Junfeng Wang;M. Teng
UBIG和Coq3(真核生物中的同源基因)是一种SAM-MTase(S-腺苷蛋氨酸依赖甲基转移酶)，它们催化原核生物到真核生物辅酶Q生物合成过程中的两个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，我们报道了UBIG/Coq3定义了一类新的膜结合蛋白。大肠杆菌UBIG与含有磷脂酰甘油(PG)或二磷脂酰甘油(CL)的脂质体特异结合，而人和酵母Coq3对富含CL的脂质体表现出强烈的偏好，CL是线粒体膜的标志性脂类。从大肠杆菌中提取的UBIG的晶体结构被测定为2.1？(1？=0.1 nm)的分辨率。该结构显示出典型的I类SAM-MTase折叠，具有几种变异，包括在链β5和螺旋α10之间的唯一插入。这种插入是高度保守的，是膜结合所必需的。关键残基的突变使得UBIG在体外不能有效结合脂质体，突变体在体内也不能挽救ΔUBIG株的表型。综上所述，我们的结果揭示了UBIG/Coq3蛋白的一种新的生化功能。
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.