title: Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Cobbold
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.|Department of Biochemistry and Molecular Biology, Department of Chemistry, Center for Malaria Research and Center for Infectious Disease Dynamics, W126 Millennium Science Complex, Pennsylvania State University, State College, PA 16802, USA.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Santos
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.|Center for Statistics and Machine Learning, Princeton University, Princeton, NJ 08544.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ochoa
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.|Department of Molecular Biology, Princeton University, Princeton, NJ 08544.|Department of Chemistry Princeton University, Princeton, NJ 08544.|Collaborative Proteomics and Mass Spectrometry Center, Princeton University, Princeton, NJ 08544.
authors.forename: David H
authors.initials: DH
authors.lastname: Perlman
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.|Department of Molecular Biology, Princeton University, Princeton, NJ 08544.|Department of Biochemistry and Molecular Biology, Department of Chemistry, Center for Malaria Research and Center for Infectious Disease Dynamics, W126 Millennium Science Complex, Pennsylvania State University, State College, PA 16802, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Llinás
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000378:metabolism; D063990:Gene Ontology; D008239:Lysine / Q000378:metabolism*; D010961:Plasmodium / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism; D056510:Position-Specific Scoring Matrices; D014176:Protein Biosynthesis; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015800:Protozoan Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D020543:Proteome; D015800:Protozoan Proteins; D008239:Lysine
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