The TLDc [Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic] domain is associated with oxidation-resistance related functions and is well conserved among eukaryotes. Seven proteins possess a TLDc domain in humans, notably proteins belonging to the oxidation resistance protein (OXR), nuclear receptor coactivator 7 (NCOA7) and TBC1 domain family member 24 (TBC1D24) families. Although the mechanism is unknown, a protective role of TLDc proteins against oxidative stress, notably in the brain, has been demonstrated. Neurobiological disorders caused by mutations in the TLDc domain have also been reported. The human NCOA7 gene encodes several mRNA isoforms; among these, isoform 4, named NCOA7-AS, is up-regulated by type 1 interferon in response to viral infection. NCOA7 and NCOA7-AS both interact with several subunits of the vacuolar proton pump V-ATPase, which leads to increased acidification of the endolysosomal system and consequently impairs infection by viruses that enter their host cells through the endosomal pathway, such as influenza A virus and hepatitis C virus. Similarly to full-length NCOA7, NCOA7-AS possesses a TLDc domain in its C-terminus. Structures of TLDc domains have been reported from zebrafish and fly but not from humans. Here, the expression, purification and crystallization of the TLDc domain from NCOA7 and NCOA7-AS is reported. The crystal structure solved at 1.8 Å resolution is compared with previously solved three-dimensional structures of TLDc domains.

中文翻译：

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人 NCOA7-AS TLDc 结构域的晶体结构

TLDc [Tre2/Bub2/Cdc16 (TBC)、溶素基序 (LysM)、催化结构域] 结构域与抗氧化相关功能相关，并且在真核生物中高度保守。人类中有 7 种蛋白质具有 TLDc 结构域，特别是属于抗氧化蛋白 (OXR)、核受体辅激活蛋白 7 (NCOA7) 和 TBC1 结构域家族成员 24 (TBC1D24) 家族的蛋白质。尽管其机制尚不清楚，但 TLDc 蛋白对氧化应激（尤其是大脑中的氧化应激）的保护作用已被证明。由 TLDc 结构域突变引起的神经生物学疾病也有报道。人类NCOA7基因编码多种 mRNA 亚型；其中，名为NCOA7-AS 的异构体 4在病毒感染时被 1 型干扰素上调。NCOA7 和 NCOA7-AS 均与液泡质子泵 V-ATP 酶的多个亚基相互作用，导致内溶酶体系统酸化增加，从而损害通过内体途径进入宿主细胞的病毒（例如甲型流感病毒和流感病毒）的感染。丙型肝炎病毒。与全长 NCOA7 类似，NCOA7-AS 在其 C 末端具有 TLDc 结构域。斑马鱼和苍蝇的 TLDc 结构域结构已有报道，但人类尚未报道过。在此，报道了来自 NCOA7 和 NCOA7-AS 的 TLDc 结构域的表达、纯化和结晶。将在 1.8 Å 分辨率下求解的晶体结构与之前求解的 TLDc 域的三维结构进行比较。