bims-toxgon 2022-09-04 papers

Issue of 2022‒09‒04
two papers selected by
Lakesh Kumar
BITS Pilani

Front Cell Infect Microbiol. 2022 ;12 947039

The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii.

Yimin Yang, Mi Lin, Xueqiu Chen, XianFeng Zhao, Lulu Chen, Mingxiu Zhao, Chaoqun Yao, Kaiyin Sheng, Yi Yang, Guangxu Ma, Aifang Du.

Toxoplasmosis caused by the protozoan Toxoplasma gondii is one of the most common parasitic diseases in humans and almost all warm-blooded animals. Lys, Glu, and Gln-specific tRNAs contain a super-modified 2-thiourea (s2U) derivatives at the position 34, which is essential for all living organisms by maintaining the structural stability and aminoacylation of tRNA, and the precision and efficiency of codon recognition during protein translation. However, the enzyme(s) involved in this modification in T. gondii remains elusive. In this report, three putative tRNA-specific 2-thiolation enzymes were identified, of which two were involved in the s2U34 modification of tRNALys, tRNAGlu, and tRNAGln. One was named TgMnmA, an apicoplast-located tRNA-specific 2-thiolation enzyme in T. gondii. Knockout of TgMnmA showed that this enzyme is important for the lytic cycle of tachyzoites. Loss of TgMnmA also led to abnormities in apicoplast biogenesis and severely disturbed apicoplast genomic transcription. Notably, mice survived from the infection with 10 TgMnmA-KO RH tachyzoites. These findings provide new insights into s2U34 tRNA modification in Apicomplexa, and suggest TgMnmA, the first apicoplast tRNA thiouridylase identified in all apicomplexans, as a potential drug target.

Keywords: 2-thiouridylase; TgMnmA; Toxoplasma gondii; apicoplast; s2U34 tRNA modification

DOI: https://doi.org/10.3389/fcimb.2022.947039

Acta Crystallogr D Struct Biol. 2022 Sep 01. 78(Pt 9): 1110-1119

Structural basis for the acetylation mechanism of the Legionella effector VipF.

Tao Tao Chen, Yanling Lin, Shijun Zhang, Aidong Han.

The pathogen Legionella pneumophila, which is the causative agent of Legionnaires' disease, secrets hundreds of effectors into host cells via its Dot/Icm secretion system to subvert host-cell pathways during pathogenesis. VipF, a conserved core effector among Legionella species, is a putative acetyltransferase, but its structure and catalytic mechanism remain unknown. Here, three crystal structures of VipF in complex with its cofactor acetyl-CoA and/or a substrate are reported. The two GNAT-like domains of VipF are connected as two wings by two β-strands to form a U-shape. Both domains bind acetyl-CoA or CoA, but only in the C-terminal domain does the molecule extend to the bottom of the U-shaped groove as required for an active transferase reaction; the molecule in the N-terminal domain folds back on itself. Interestingly, when chloramphenicol, a putative substrate, binds in the pocket of the central U-shaped groove adjacent to the N-terminal domain, VipF remains in an open conformation. Moreover, mutations in the central U-shaped groove, including Glu129 and Asp251, largely impaired the acetyltransferase activity of VipF, suggesting a unique enzymatic mechanism for the Legionella effector VipF.

Keywords: Legionella pneumophila; Legionnaires' disease; VipF; acetyltransferases; core effectors

DOI: https://doi.org/10.1107/S2059798322007318