Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications.
Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications.
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人类 gephyrin 和植物 Cnx1 G 结构域的晶体结构：比较分析和功能意义。
DOI：
10.1006/jmbi.2001.4952
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发表时间：
2001
影响因子：
5.6
通讯作者：
Schindelin,H
中科院分区：
文献类型：
--
作者：
Schwarz,G;Schrader,N;Mendel,RR;Hecht,HJ;Schindelin,H
钼辅因子（Moco）由独特且保守的蝶呤衍生物组成，其通常被称为蝶呤（MPT），其与必需的过渡金属钼（Mo）配位。除了固氮酶之外，所有钼酶的酶活性都需要Moco，并且Moco是通过依赖于至少六种基因产物的活性的进化古老的多步途径合成的。在真核生物中，Moco生物合成的最后一步，即Mo转移和插入到MPT中，由植物中的双结构域蛋白Cnx 1和哺乳动物中的桥蛋白催化。桥蛋白是普遍表达的，并且最初在中枢神经系统中发现，在中枢神经系统中，桥蛋白对于突触后膜中抑制性神经受体的聚集是必需的。桥蛋白和Cnx 1含有至少两个功能结构域（E和G），其与大肠杆菌蛋白MoeA和莫加同源，其原子结构最近已被解决。在这里，我们提出的N-末端的人桥蛋白G结构域（Geph-G）和C-末端的拟南芥Cnx 1 G结构域（Cnx 1-G）的晶体结构，在1.7和2.6微分辨率，分别。这些结构与莫加高度相似，并与它们的三维结构进行了比较，揭示了它们的四个主要差异：（1）在Geph-G和Cnx 1-G中，在莫加的第一个β-链和α-螺旋之间存在额外的α-螺旋。(2)α2和β2之间的环在所有三种结构中都经历构象变化。(3)在莫加中发现的β-发夹环在Geph-G和Cnx 1-G中不存在。(4)Geph-G的C末端遵循与莫加不同的路径。根据真核生物蛋白质的结构及其与大肠杆菌蛋白质结构的比较，coli莫加中，进一步完善了MPT的预测结合位点。此外，特征的选择性剪接变异体的桥蛋白的Geph-G的三维结构的背景下进行了分析。
The molybdenum cofactor (Moco) consists of a unique and conserved pterin derivative, usually referred to as molybdopterin (MPT), which coordinates the essential transition metal molybdenum (Mo). Moco is required for the enzymatic activities of all Mo-enzymes, with the exception of nitrogenase and is synthesized by an evolutionary old multi-step pathway that is dependent on the activities of at least six gene products. In eukaryotes, the final step of Moco biosynthesis, i.e. transfer and insertion of Mo into MPT, is catalyzed by the two-domain proteins Cnx1 in plants and gephyrin in mammals. Gephyrin is ubiquitously expressed, and was initially found in the central nervous system, where it is essential for clustering of inhibitory neuroreceptors in the postsynaptic membrane. Gephyrin and Cnx1 contain at least two functional domains (E and G) that are homologous to the Escherichia coli proteins MoeA and MogA, the atomic structures of which have been solved recently. Here, we present the crystal structures of the N-terminal human gephyrin G domain (Geph-G) and the C-terminal Arabidopsis thaliana Cnx1 G domain (Cnx1-G) at 1.7 and 2.6 Å resolution, respectively. These structures are highly similar and compared to MogA reveal four major differences in their three-dimensional structures: (1) In Geph-G and Cnx1-G an additional α-helix is present between the first β-strand and α-helix of MogA. (2) The loop between α2 and β2 undergoes conformational changes in all three structures. (3) A β-hairpin loop found in MogA is absent from Geph-G and Cnx1-G. (4) The C terminus of Geph-G follows a different path from that in MogA. Based on the structures of the eukaryotic proteins and their comparisons with E. coli MogA, the predicted binding site for MPT has been further refined. In addition, the characterized alternative splice variants of gephyrin are analyzed in the context of the three-dimensional structure of Geph-G.