National Institute of Biological Sciences, Beijing, China.
PLoS One. 2011;6(9):e24790. doi: 10.1371/journal.pone.0024790. Epub 2011 Sep 16.
The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into seven major types with a wide distribution throughout the three domains of life. The type 1 protein mitoNEET has been shown to fold into a dimer with the signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of all other types of CISDs were unknown. Here we report the crystal structures of type 3, 4, and 6 CISDs determined at 1.5 Å, 1.8 Å and 1.15 Å resolution, respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a dimeric structure. Although similar to each other, the two structures have permutated topologies, and both are distinct from the type 1 structure. The type 6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an internal pseudo dyad symmetry. All currently known CISD structures share dual iron-sulfur binding modules and a β-sandwich for either intermolecular or intramolecular dimerization. The iron-sulfur binding module, the β-strand N-terminal to the module and a proline motif are conserved among different type structures, but the dimerization module and the interface and orientation between the two iron-sulfur binding modules are divergent. Sequence analysis further shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings suggest that all CISDs share common ancestry and diverged into three primary folds with a characteristic phylogenetic distribution: a eukaryote-specific fold adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3, 4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our comprehensive structural, sequential and phylogenetic analysis provides significant insight into the assembly principles and evolutionary relationship of CISDs.
最近发现的 CDGSH 铁硫结构域（CISD）分为七大类，广泛分布于生命的三个域。已证明具有特征性 CDGSH 模体的 1 型蛋白 mitoNEET 折叠成二聚体，该模体结合 [2Fe-2S]簇。然而，所有其他类型的 CISD 结构都未知。在这里，我们报告了分别以 1.5Å、1.8Å 和 1.15Å分辨率确定的 3 型、4 型和 6 型 CISD 的晶体结构。3 型和 4 型 CISD 每个都包含一个 CDGSH 模体，并采用二聚体结构。尽管彼此相似，但两种结构具有置换拓扑结构，且均与 1 型结构不同。6 型 CISD 包含串联 CDGSH 模体，采用单体结构，具有内部拟二分对称。目前所有已知的 CISD 结构都共享双铁硫结合模块和用于分子间或分子内二聚化的β-三明治。铁硫结合模块、模块的 N 端β-链和脯氨酸模体在不同类型的结构中是保守的，但二聚化模块以及两个铁硫结合模块之间的接口和方向是不同的。序列分析进一步表明 CISD 类型 4 和 7 之间以及 1 和 2 之间存在相似性。我们的研究结果表明，所有 CISD 都具有共同的祖先，并分为三个主要折叠，具有特征性的系统发育分布：1 型和 2 型蛋白采用的真核生物特异性折叠，3 型、4 型和 7 型蛋白采用的原核生物特异性折叠，以及 5 型和 6 型蛋白采用的串联模体折叠。我们全面的结构、序列和系统发育分析为 CISD 的组装原则和进化关系提供了重要的见解。
