Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite

Scientific Reports
Simon A CobboldManuel Llinas

Abstract

Lysine acetylation is a ubiquitous post-translational modification in many organisms including the malaria parasite Plasmodium falciparum, yet the full extent of acetylation across the parasite proteome remains unresolved. Moreover, the functional significance of acetylation or how specific acetyl-lysine sites are regulated is largely unknown. Here we report a seven-fold expansion of the known parasite 'acetylome', characterizing 2,876 acetylation sites on 1,146 proteins. We observe that lysine acetylation targets a diverse range of protein complexes and is particularly enriched within the Apicomplexan AP2 (ApiAP2) DNA-binding protein family. Using quantitative proteomics we determined that artificial perturbation of the acetate/acetyl-CoA balance alters the acetyl-lysine occupancy of several ApiAP2 DNA-binding proteins and related transcriptional proteins. This metabolic signaling could mediate significant downstream transcriptional responses, as we show that acetylation of an ApiAP2 DNA-binding domain ablates its DNA-binding propensity. Lastly, we investigated the acetyl-lysine targets of each class of lysine deacetylase in order to begin to explore how each class of enzyme contributes to regulating the P. falciparum acetylome.

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Citations

Jun 16, 2017·Cell Host & Microbe·Joana Mendonca SantosManuel Llinás
Feb 15, 2018·Molecular & Cellular Proteomics : MCP·Shichang LiuNing Li
Sep 30, 2017·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Wenzheng BaoDe-Shuang Huang
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Nov 26, 2020·Molecular Microbiology·Manish KumarManoj T Duraisingh
Jan 30, 2021·Molecular and Biochemical Parasitology·Susanne SchipperJude M Przyborski
Jan 27, 2019·Experimental Parasitology·Jessica A EngelKatherine T Andrews
Jun 3, 2021·International Journal of Molecular Sciences·Maria Theresia WatzlowikGernot Längst
Jul 30, 2021·Molecular and Biochemical Parasitology·Nila Johnson, Nisha Philip
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Methods Mentioned

BETA
acetylation
histone acetylation
immunoprecipitation
the
further

Software Mentioned

ProteomeDiscoverer
HMMER
STRING
PlasmoDB
ice Logo builder
Xcalibur
Proteome
Mascot
Scaffold

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