假定的含溴结构域蛋白 5 是刚地弓形虫生长所必需的。

Hypothetical bromodomain-containing protein 5 is required for the growth of Toxoplasma gondii.

机构信息

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, China; Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Branch of Animal Husbandry and Veterinary of Heilongjiang Academy of Agricultural Sciences, Qiqihar 161000, Heilongjiang Province, China.

Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

出版信息

Vet Parasitol. 2022 Sep;309:109767. doi: 10.1016/j.vetpar.2022.109767. Epub 2022 Jul 22.

DOI:10.1016/j.vetpar.2022.109767

PMID:35901606

Abstract

Bromodomain (BRD) is a highly conserved structural module domain, found in various proteins, including chromatin-related proteins, nucleus acetyltransferases, and transcription-associated proteins. Toxoplasma gondii, a zoonotic protozoan, encodes at least 12 predicted BRD-containing proteins (BDPs). Here, we investigated the subcellular location and regulatory role of a hypothetical protein BDP that we named TgBDP5. The BRD of TgBDP5 did not contain the conserved Asn and Tyr residues required for acetyl-lysine recognition. TgBDP5 localized in the nucleus of the parasite and remained unchanged during parasite replication. Conditional ablation of TgBDP5 through an auxin-inducible degron-based knockdown strategy caused a growth defect in parasite replication. Depletion of TgBDP5 led to changes in the expression level of 179 genes, suggesting it as an important target for drugs acting against T. gondii.

摘要

溴结构域（BRD）是一种高度保守的结构模块域，存在于各种蛋白质中，包括染色质相关蛋白、核乙酰转移酶和转录相关蛋白。刚地弓形虫是一种人畜共患的原生动物，编码至少 12 种预测含有 BRD 的蛋白质（BDP）。在这里，我们研究了一种假设蛋白 TgBDP5 的亚细胞定位和调节作用，我们将其命名为 TgBDP5。TgBDP5 的 BRD 不包含乙酰-赖氨酸识别所需的保守的 Asn 和 Tyr 残基。TgBDP5 定位于寄生虫的细胞核中，在寄生虫复制过程中保持不变。通过基于生长素诱导的降解结构域的敲低策略条件性敲除 TgBDP5 会导致寄生虫复制的生长缺陷。TgBDP5 的耗竭导致 179 个基因的表达水平发生变化，表明它是针对弓形虫的药物的重要靶标。