Institut Pasteur, Université de Paris, Biologie des Bactéries Intracellulaires , Paris, France.
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon, Saskatchewan, Canada.
mBio. 2023 Oct 31;14(5):e0165523. doi: 10.1128/mbio.01655-23. Epub 2023 Oct 5.
is an intracellular bacterium responsible of Legionnaires' disease, a severe pneumonia that is often fatal when not treated promptly. The pathogen's ability to efficiently colonize the host resides in its ability to replicate intracellularly. Essential for intracellular replication is translocation of many different protein effectors a specialized secretion system. One of them, called RomA, binds and directly modifies the host chromatin at a unique site (tri-methylation of lysine 14 of histone H3 [H3K14me]). However, the molecular mechanisms of binding are not known. Here, we resolve this question through structural characterization of RomA together with the H3 peptide. We specifically reveal an active role of the ankyrin repeats located in its C-terminal in the interaction with the histone H3 tail. Indeed, without the ankyrin domains, RomA loses its ability to act as histone methyltransferase. These results discover the molecular mechanisms by which a bacterial histone methyltransferase that is conserved in strains acts to modify chromatin.
是一种细胞内细菌，可导致军团病，这是一种严重的肺炎，如果不及时治疗，通常是致命的。病原体在宿主中高效定殖的能力源于其在细胞内复制的能力。对于细胞内复制而言，关键是多种不同的蛋白效应子的易位，这需要一个专门的分泌系统。其中一种叫做 RomA，可在独特的位点（组蛋白 H3 的赖氨酸 14 的三甲基化 [H3K14me]）上结合并直接修饰宿主染色质。然而，结合的分子机制尚不清楚。在这里，我们通过 RomA 与 H3 肽的结构特征解析解决了这个问题。我们特别揭示了位于其 C 末端的锚蛋白重复在与组蛋白 H3 尾部相互作用中的积极作用。实际上，如果没有锚蛋白结构域，RomA 就会失去作为组蛋白甲基转移酶的作用。这些结果揭示了一种在 菌株中保守的细菌组蛋白甲基转移酶修饰染色质的分子机制。
