Tryptophan synthase catalyzes the last two steps of tryptophan biosynthesis in plants, fungi and bacteria. It consists of two protein chains, designated α and β, encoded by trpA and trpB genes, that function as an αββα complex. Structural and functional features of tryptophan synthase have been extensively studied, explaining the roles of individual residues in the two active sites in catalysis and allosteric regulation. TrpA serves as a model for protein-folding studies. In 1969, Jackson and Yanofsky observed that the typically monomeric TrpA forms a small population of dimers. Dimerization was postulated to take place through an exchange of structural elements of the monomeric chains, a phenomenon later termed 3D domain swapping. The structural details of the TrpA dimer have remained unknown. Here, the crystal structure of the Streptococcus pneumoniae TrpA homodimer is reported, demonstrating 3D domain swapping in a TIM-barrel fold for the first time. The N-terminal domain comprising the H0-S1-H1-S2 elements is exchanged, while the hinge region corresponds to loop L2 linking strand S2 to helix H2'. The structural elements S2 and L2 carry the catalytic residues Glu52 and Asp63. As the S2 element is part of the swapped domain, the architecture of the catalytic apparatus in the dimer is recreated from two protein chains. The homodimer interface overlaps with the α-β interface of the tryptophan synthase αββα heterotetramer, suggesting that the 3D domain-swapped dimer cannot form a complex with the β subunit. In the crystal, the dimers assemble into a decamer comprising two pentameric rings.

中文翻译：

---

肺炎链球菌色氨酸合酶 α 亚基 TIM 桶中的 3D 结构域交换。


色氨酸合酶催化植物、真菌和细菌中色氨酸生物合成的最后两个步骤。它由两条蛋白质链组成，分别称为 α 和 β，由 trpA 和 trpB 基因编码，作为 αββα 复合物发挥作用。色氨酸合酶的结构和功能特征已被广泛研究，解释了两个活性位点中各个残基在催化和变构调节中的作用。 TrpA 作为蛋白质折叠研究的模型。 1969 年，Jackson 和 Yanofsky 观察到典型的单体 TrpA 形成了一小群二聚体。假设二聚化是通过单体链结构元素的交换而发生的，这种现象后来被称为 3D 结构域交换。 TrpA 二聚体的结构细节仍然未知。在此，报道了肺炎链球菌 TrpA 同二聚体的晶体结构，首次证明了 TIM 桶状折叠中的 3D 结构域交换。包含 H0-S1-H1-S2 元件的 N 端结构域被交换，而铰链区对应于将链 S2 连接到螺旋 H2' 的环 L2。结构元件S2和L2带有催化残基Glu52和Asp63。由于 S2 元件是交换结构域的一部分，因此二聚体中催化装置的结构是从两条蛋白质链重建的。同源二聚体界面与色氨酸合酶αββα异四聚体的α-β界面重叠，表明3D结构域交换二聚体不能与β亚基形成复合物。在晶体中，二聚体组装成包含两个五聚环的十聚体。