The crystal structure of Escherichia coli MoeA and its relationship to the multifunctional protein gephyrin.
The crystal structure of Escherichia coli MoeA and its relationship to the multifunctional protein gephyrin.
复制标题
大肠杆菌MoeA的晶体结构及其与多功能蛋白gephyrin的关系。
DOI：
10.1016/s0969-2126(01)00588-3
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Schindelin,H
中科院分区：
文献类型：
--
作者：
Xiang,S;Nichols,J;Rajagopalan,KV;Schindelin,H
背景：钼辅因子（Moco）生物合成是古细菌、真细菌和真核生物中进化上保守的途径。在人类中，生物合成途径的遗传异常导致Moco缺乏症，伴随着严重的神经系统症状和出生后不久的死亡。大肠杆菌MoeA和莫加蛋白参与了Moco生物合成的最后一步：将钼掺入到Moco的有机吡喃蝶呤（MPT）中。coliMoeA已经在2 μ m分辨率下进行了改进，并揭示了高度伸长的MoeA单体由四个明显分离的结构域组成，其中一个结构域与莫加结构相关，表明两种蛋白质之间存在不同的进化关系。MoeA的活性形式是一个二聚体，和一个推定的活性位点似乎是本地化的第一个单体的结构域II和结构域III和IV的第二个monomer.Conclusions之间形成的裂缝：在真核生物中，莫加和MoeA融合成一个单一的多肽链。相应的哺乳动物蛋白质桥蛋白也涉及甘氨酸能受体在抑制性突触处锚定到细胞骨架。基于MoeA和莫加的结构，推测桥卟啉是一个高度有序的分子，至少含有5个结构域。这种多结构域的排列可以为其功能多样性提供结构基础。MoeA和莫加的寡聚状态表明桥蛋白如何在抑制性突触处组装成六边形支架。
Background:Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway present in archaea, eubacteria, and eukaryotes. In humans, genetic abnormalities in the biosynthetic pathway result in Moco deficiency, which is accompanied by severe neurological symptoms and death shortly after birth. TheEscherichia coliMoeA and MogA proteins are involved in the final step of Moco biosynthesis: the incorporation of molybdenum into molybdopterin (MPT), the organic pyranopterin moiety of Moco.Results:The crystal structure ofE. coliMoeA has been refined at 2 Å resolution and reveals that the highly elongated MoeA monomer consists of four clearly separated domains, one of which is structurally related to MogA, indicating a divergent evolutionary relationship between both proteins. The active form of MoeA is a dimer, and a putative active site appears to be localized to a cleft formed between domain II of the first monomer and domains III and IV of the second monomer.Conclusions:In eukaryotes, MogA and MoeA are fused into a single polypeptide chain. The corresponding mammalian protein gephyrin has also been implicated in the anchoring of glycinergic receptors to the cytoskeleton at inhibitory synapses. Based on the structures of MoeA and MogA, gephyrin is surmised to be a highly organized molecule containing at least five domains. This multidomain arrangement could provide a structural basis for its functional diversity. The oligomeric states of MoeA and MogA suggest how gephyrin could assemble into a hexagonal scaffold at inhibitory synapses.