首页|Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

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The biology of Toxoplasma gondii,the causative pathogen of one of the most widespread parasitic diseases(toxoplasmosis),remains poorly understood.Lactate,which is derived from glu-cose metabolism,is not only an energy source in a variety of organisms,including T.gondii,but also a regulatory molecule that participates in gene activation and protein function.Lysine lactylation(Kla)is a type of post-translational modifications(PTMs)that has been recently associated with chromatin remodeling;however,K1a of histone and non-histone proteins has not yet been studied in T.gondii.To examine the prevalence and function of lactylation in T.gondii parasites,we mapped the lactylome of proliferating tachyzoite cells and identified 1964 K1a sites on 955 proteins in the T.gondii RH strain.Lactylated proteins were distributed in multiple subcellular compart-ments and were closely related to a wide variety of biological processes,including mRNA splicing,glycolysis,aminoacyl-tRNA biosynthesis,RNA transport,and many signaling pathways.We also performed a chromatin immunoprecipitation sequencing(ChIP-seq)analysis using a lactylation-specific antibody and found that the histones H4K121a and H3K141a were enriched in the promoter and exon regions of T.gondii associated with microtubule-based movement and cell invasion.We further confirmed the delactylase activity of histone deacetylases TgHDAC2-4,and found that treatment with anti-histone acetyltransferase(TgMYST-A)antibodies profoundly reduced protein lactylation in T.gondii.This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T.gondii.

Toxoplasma gondiiLactylationProtein post-translational modificationMetabolismChIP-seq

Deqi Yin、Ning Jiang、Chang Cheng、Xiaoyu Sang、Ying Feng、Ran Chen、Qijun Chen

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Key Laboratory of Livestock Infectious Diseases in Northeast China,Ministry of Education,Key Laboratory of Zoonosis,College of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang 110166,China

The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites,Chinese Academy of Medical Sciences,Shenyang 110866,China

National Key R&D Program of ChinaNational Key R&D Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCAMS Innovation Fund for Medical Sciences(CIFMS)

2017YFD05004002017YFD050120031972702817722192019-I2M-5-042

2023

基因组蛋白质组与生物信息学报(英文版)
中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报(英文版)

CSTPCDCSCD
影响因子:0.495
ISSN:1672-0229
年,卷(期):2023.6(6)
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