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

Simon A. Cobbold, Joana M. Santos, Alejandro Ochoa, David H. Perlman, Manuel Llinas

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 DNAbinding 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.

Original languageEnglish (US)
Article number19722
JournalScientific reports
Volume6
DOIs
StatePublished - Jan 27 2016

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite'. Together they form a unique fingerprint.

Cite this