TgMAP1c is involved in apicoplast biogenesis in Toxoplasma gondii.


Journal

International journal for parasitology
ISSN: 1879-0135
Titre abrégé: Int J Parasitol
Pays: England
ID NLM: 0314024

Informations de publication

Date de publication:
06 2020
Historique:
received: 12 12 2019
revised: 02 03 2020
accepted: 09 03 2020
pubmed: 8 5 2020
medline: 27 8 2021
entrez: 8 5 2020
Statut: ppublish

Résumé

Methionine aminopeptidases (MAPs), which remove the N-terminal methionine from newly synthesised proteins, are present in all life forms. Three type I MAPs and one type II MAP are encoded in the genome of Toxoplasma gondii. In this study, we found that the inducible knockdown of each type I TgMAP (TgMAP1a-c) reduced the growth and proliferation of the parasite significantly. Among them, TgMAP1c was found to be localised to the apicoplast of the parasite. Inducible knockdown of TgMAP1c led to a defect in the abundance of apicoplast-encoded transcripts, and a later reduction in the apicoplast genome copy number and loss of the apicoplast structure. This finding indicates that transcription of the apicoplast genome was impaired upon knockdown of TgMAP1c. We also found that the function of TgMAP1c in apicoplast biogenesis depends on its enzymatic domain. Expression of a recombinant protein in which the active domain of TgMAP1c was replaced with that of TgMAP1a or TgMAP1b could not restore the defective growth and replication phenotype caused by knockdown of TgMAP1c, indicating that these three enzymes have distinct substrate preferences. An in vitro analysis also revealed that TgMAP1c is an active enzyme that acts specifically on the substrate H-Met-p-NA. In addition, inducible knockdown of TgMAP1c reduced the virulence of T. gondii in mice. Taken together, these results demonstrate that TgMAP1c plays a key role in the biogenesis and maintenance of the T. gondii apicoplast.

Identifiants

pubmed: 32380097
pii: S0020-7519(20)30095-3
doi: 10.1016/j.ijpara.2020.03.004
pii:
doi:

Substances chimiques

Protozoan Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

487-499

Informations de copyright

Copyright © 2020 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Auteurs

Jun Zheng (J)

Division of Fundamental Immunology, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 678 Haping Street, Harbin 150069, People's Republic of China.

Wenqiang Su (W)

Division of Fundamental Immunology, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 678 Haping Street, Harbin 150069, People's Republic of China.

Shinuo Cao (S)

Division of Fundamental Immunology, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 678 Haping Street, Harbin 150069, People's Republic of China.

Zhaoxia Zhang (Z)

Division of Fundamental Immunology, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 678 Haping Street, Harbin 150069, People's Republic of China.

Cheng Du (C)

Division of Fundamental Immunology, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 678 Haping Street, Harbin 150069, People's Republic of China.

Honglin Jia (H)

Division of Fundamental Immunology, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 678 Haping Street, Harbin 150069, People's Republic of China. Electronic address: jiahonglin@caas.cn.

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Classifications MeSH