Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii  

作　　者：Deqi Yin Ning Jiang Chang Cheng Xiaoyu Sang Ying Feng Ran Chen Qijun Chen 

机构地区：[1]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 [2]The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites,Chinese Academy of Medical Sciences,Shenyang 110866,China

出　　处：《Genomics, Proteomics & Bioinformatics》2023年第6期1163-1181,共19页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by grants from the National Key R&D Program of China(Grant Nos.2017YFD0500400 and 2017YFD0501200);the National Natural Science Foundation of China(Grant Nos.31972702 and 81772219);the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2019-I2M-5-042).

摘　　要：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 glucose 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,Kla 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 Kla sites on 955 proteins in the T.gondii RH strain.Lactylated proteins were distributed in multiple subcellular compartments 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 lactylationspecific antibody and found that the histones H4K12la and H3K14la 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.

关 键 词：Toxoplasmagondit Lactylation Proteinpost-translational modification METABOLISM CHIP-SEQ 

分 类 号：Q945[生物学—植物学]