World Malaria Report (WHO, 2023).
Cowell, A. & Winzeler, E. Exploration of the Plasmodium falciparum resistome and druggable genome reveals new mechanisms of drug resistance and antimalarial targets. Microbiol. Insights 11, 1178636118808529 (2018).
Wicht, K. J., Mok, S. & Fidock, D. A. Molecular mechanisms of drug resistance in Plasmodium falciparum malaria. Annu. Rev. Microbiol. 74, 431–454 (2020).
Global Technical Strategy For Malaria 2016–2030, 2021 Update (WHO, 2021).
Siqueira-Neto, J. L. et al. Antimalarial drug discovery: progress and approaches. Nat. Rev. Drug Discov. 22, 807–826 (2023).
Guttery, D. S. et al. Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation. Cell Host Microbe 16, 128–140 (2014).
Singh, G. & Gupta, D. In-silico functional annotation of Plasmodium falciparum hypothetical proteins to identify novel drug targets. Front. Genet. 13, 821516 (2022).
Wasmuth, J., Daub, J., Peregrín-Alvarez, J. M., Finney, C. A. M. & Parkinson, J. The origins of apicomplexan sequence innovation. Genome Res. 19, 1202–1213 (2009).
Niss, K. et al. Complete topological mapping of a cellular protein interactome reveals bow-tie motifs as ubiquitous connectors of protein complexes. Cell Rep. 31, 107763 (2020).
Fadhal, E., Gamieldien, J. & Mwambene, E. C. Protein interaction networks as metric spaces: a novel perspective on distribution of hubs. BMC Syst. Biol. 8, 6 (2014).
Birth, D., Kao, W.-C. & Hunte, C. Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action. Nat. Commun. 5, 4029 (2014).
Silk, S. E. et al. Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial. Lancet 24, 1105–1117 (2024).
Keeley, A. & Soldati, D. The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa. Trends Cell Biol. 14, 528–532 (2004).
Ghosh, S. et al. The Plasmodium rhoptry associated protein complex is important for parasitophorous vacuole membrane structure and intraerythrocytic parasite growth. Cell. Microbiol. 19, e12733 (2017).
Pasternak, M. et al. RhopH2 and RhopH3 export enables assembly of the RhopH complex on P. falciparum-infected erythrocyte membranes. Commun. Biol. 5, 333 (2022).
Cao, J. et al. Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites. Parasitol. Int. 58, 29–35 (2009).
Chugh, M. et al. Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum. Proc. Natl Acad. Sci. USA 110, 5392–5397 (2013).
Ho, C.-M. et al. Malaria parasite translocon structure and mechanism of effector export. Nature 561, 70–75 (2018).
Morano, A. A., Rudlaff, R. M. & Dvorin, J. D. A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum. Nat. Commun. 14, 3916 (2023).
Fields, S. & Song, O. A novel genetic system to detect protein–protein interactions. Nature 340, 245–246 (1989).
LaCount, D. J. et al. A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438, 103–107 (2005).
Gavin, A.-C. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141–147 (2002).
Wessels, H. J. C. T. et al. LC-MS/MS as an alternative for SDS-PAGE in blue native analysis of protein complexes. Proteomics 9, 4221–4228 (2009).
Hillier, C. et al. Landscape of the Plasmodium interactome reveals both conserved and species-specific functionality. Cell Rep. 28, 1635–1647.e5 (2019).
Martinez Molina, D. et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science 341, 84–87 (2013).
Savitski, M. M. et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science 346, 1255784 (2014).
Dziekan, J. M. et al. Cellular thermal shift assay for the identification of drug–target interactions in the Plasmodium falciparum proteome. Nat. Protoc. 15, 1881–1921 (2020).
Tan, C. S. H. et al. Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells. Science 359, 1170–1177 (2018).
Becher, I. et al. Pervasive protein thermal stability variation during the cell cycle. Cell 173, 1495–1507.e18 (2018).
Hashimoto, Y., Sheng, X., Murray-Nerger, L. A. & Cristea, I. M. Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection. Nat. Commun. 11, 806 (2020).
Justice, J. L. et al. Systematic profiling of protein complex dynamics reveals DNA-PK phosphorylation of IFI16 en route to herpesvirus immunity. Sci. Adv. 7, eabg6680 (2021).
Sun, S. et al. Improved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation. Nat. Commun. 14, 7697 (2023).
Reed, T. J., Tyl, M. D., Tadych, A., Troyanskaya, O. G. & Cristea, I. M. Tapioca: a platform for predicting de novo protein–protein interactions in dynamic contexts. Nat. Methods 21, 488–500 (2024).
Pasini, E. M. et al. In-depth analysis of the membrane and cytosolic proteome of red blood cells. Blood 108, 791–801 (2006).
Bryk, A. H. & Wiśniewski, J. R. Quantitative analysis of human red blood cell proteome. J. Proteome Res. 16, 2752–2761 (2017).
Pazicky, S. P. falciparum MAPX models, timepoints 4–22 hpi. Zenodo https://doi.org/10.5281/ZENODO.13859621 (2025).
Huang, H. & Bader, J. S. Precision and recall estimates for two-hybrid screens. Bioinformatics 25, 372–378 (2009).
Li, B., Altelaar, M. & van Breukelen, B. Identification of protein complexes by integrating protein abundance and interaction features using a deep learning strategy. Int. J. Mol. Sci. 24, 7884 (2023).
Wong, W. et al. Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. eLife 3, e03080 (2014).
Sun, M. et al. Dynamical features of the Plasmodium falciparum ribosome during translation. Nucleic Acids Res. 43, 10515–10524 (2015).
Wong, W. et al. The antimalarial Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nat. Microbiol. 2, 17031 (2017).
Holder, A. A., Freeman, R. R., Uni, S. & Aikawa, M. Isolation of a Plasmodium falciparum rhoptry protein. Mol. Biochem. Parasitol. 14, 293–303 (1985).
Cooper, J. A. et al. The 140/130/105 kilodalton protein complex in the rhoptries of Plasmodium falciparum consists of discrete polypeptides. Mol. Biochem. Parasitol. 29, 251–260 (1988).
Takebe, S., Witola, W. H., Schimanski, B., Günzl, A. & Ben Mamoun, C. Purification of components of the translation elongation factor complex of Plasmodium falciparum by tandem affinity purification. Eukaryot. Cell 6, 584–591 (2007).
Tellier, G. et al. Identification of Plasmodium falciparum translation initiation eIF2β subunit: direct interaction with protein phosphatase type 1. Front. Microbiol. 7, 777 (2016).
Dastidar, E. G. et al. Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway. BMC Biol. 10, 5 (2012).
Jaramillo Ponce, J. R., Kapps, D., Paulus, C., Chicher, J. & Frugier, M. Discovery of two distinct aminoacyl-tRNA synthetase complexes anchored to the Plasmodium surface tRNA import protein. J. Biol. Chem. 298, 101987 (2022).
Wang, L. et al. Characterization of the 26S proteasome network in Plasmodium falciparum. Sci. Rep. 5, 17818 (2015).
Leneghan, D. & Bell, A. Immunophilin–protein interactions in Plasmodium falciparum. Parasitology 142, 1404–1414 (2015).
Garrido, M. F. et al. Regulation of eIF4F translation initiation complex by the peptidyl prolyl isomerase FKBP7 in taxane-resistant prostate cancer. Clin. Cancer Res. 25, 710–723 (2019).
Thommen, B. T. et al. Genetic validation of PfFKBP35 as an antimalarial drug target. eLife 12, RP86975 (2023).
Montemayor, E. J. et al. Molecular basis for the distinct cellular functions of the Lsm1–7 and Lsm2–8 complexes. RNA 26, 1400–1413 (2020).
Zhang, Y. et al. A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts. Nat. Commun. 11, 4509 (2020).
Menard, L., Maughan, D. & Vigoreaux, J. The structural and functional coordination of glycolytic enzymes in muscle: evidence of a metabolon? Biology 3, 623–644 (2014).
Droll, D. et al. Disruption of the RNA exosome reveals the hidden face of the malaria parasite transcriptome. RNA Biol. 15, 1206–1214 (2018).
Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).
Liu, J.-J. et al. CryoEM structure of yeast cytoplasmic exosome complex. Cell Res. 26, 822–837 (2016).
VanDemark, A. P., Hofmann, R. M., Tsui, C., Pickart, C. M. & Wolberger, C. Molecular Insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer. Cell 105, 711–720 (2001).
Carmo, O. M. S. et al. Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer’s clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1. PLOS Pathog. 18, e1009882 (2022).
Dietz, O. et al. Characterization of the small exported Plasmodium falciparum membrane protein SEMP1. PLoS ONE 9, e103272 (2014).
Das, D., Krishnan, S. R., Roy, A. & Bulusu, G. A network-based approach reveals novel invasion and Maurer’s clefts-related proteins in Plasmodium falciparum. Mol. Omics 15, 431–441 (2019).
Birnbaum, J. et al. A genetic system to study Plasmodium falciparum protein function. Nat. Methods 14, 450–456 (2017).
Heiber, A. et al. Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. PLOS Pathog. 9, e1003546 (2013).
Mesén-Ramírez, P. et al. Stable translocation intermediates jam global protein export in Plasmodium falciparum parasites and link the PTEX component EXP2 with translocation activity. PLOS Pathog. 12, e1005618 (2016).
Hawthorne, P. L. et al. A novel Plasmodium falciparum ring stage protein, REX, is located in Maurer’s clefts. Mol. Biochem. Parasitol. 136, 181–189 (2004).
Klink, B. U. et al. Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation. Proc. Natl Acad. Sci. USA 119, e2121494119 (2022).
Nordmann, M. et al. The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7. Curr. Biol. 20, 1654–1659 (2010).
Struck, N. S. et al. Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi marker PfGRASP. J. Cell Sci. 118, 5603–5613 (2005).
Krai, P., Dalal, S. & Klemba, M. Evidence for a Golgi-to-endosome protein sorting pathway in Plasmodium falciparum. PLoS ONE 9, e89771 (2014).
Kimmel, J. et al. Gene-by-gene screen of the unknown proteins encoded on Plasmodium falciparum chromosome 3. Cell Syst. 14, 9–23 (2023).
Goyal, M., Banerjee, C., Nag, S. & Bandyopadhyay, U. The Alba protein family: structure and function. Biochim. Biophys. Acta 1864, 570–583 (2016).
Jelinska, C. et al. Obligate heterodimerization of the archaeal Alba2 protein with Alba1 provides a mechanism for control of DNA packaging. Structure 13, 963–971 (2005).
Bozdech, Z. et al. The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 1, e5 (2003).
Le Roch, K. G. et al. Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301, 1503–1508 (2003).
Pease, B. N. et al. Global analysis of protein expression and phosphorylation of three stages of Plasmodium falciparum intraerythrocytic development. J. Proteome Res. 12, 4028–4045 (2013).
Foth, B. J., Zhang, N., Mok, S., Preiser, P. R. & Bozdech, Z. Quantitative protein expression profiling reveals extensive post-transcriptional regulation and post-translational modifications in schizont-stage malaria parasites. Genome Biol. 9, R177 (2008).
Foth, B. J. et al. Quantitative time-course profiling of parasite and host cell proteins in the human malaria parasite Plasmodium falciparum. Mol. Cell. Proteom. 10, M110.006411 (2011).
Kucharski, M. et al. A comprehensive RNA handling and transcriptomics guide for high-throughput processing of Plasmodium blood-stage samples. Malar. J. 19, 363 (2020).
Khacho, M. et al. eEF1A is a novel component of the mammalian nuclear protein export machinery. Mol. Biol. Cell 19, 5296 (2008).
Bunai, F., Ando, K., Ueno, H. & Numata, O. Tetrahymena eukaryotic translation elongation factor 1A (eEF1A) bundles filamentous actin through dimer formation. J. Biochem. 140, 393–399 (2006).
Chang, R. & Wang, E. Mouse translation elongation factor eEF1A-2 interacts with Prdx-I to protect cells against apoptotic death induced by oxidative stress. J. Cell. Biochem. 100, 267–278 (2007).
Carothers, D. J., Pons, G. & Patel, M. S. Dihydrolipoamide dehydrogenase: functional similarities and divergent evolution of the pyridine nucleotide-disulfide oxidoreductases. Arch. Biochem. Biophys. 268, 409–425 (1989).
DaFonseca, C. J., Shu, F. & Zhang, J. J. Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-γ. Proc. Natl Acad. Sci. USA 98, 3034–3039 (2001).
Finley, D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem. 78, 477–513 (2009).
Lenz, S. et al. Reliable identification of protein–protein interactions by crosslinking mass spectrometry. Nat. Commun. 12, 3564 (2021).
Lu, H. et al. Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials. Signal Transduct. Target. Ther. 5, 213 (2020).
Lu, Q. et al. Proteome-wide cellular thermal shift assay reveals unexpected cross-talk between brassinosteroid and auxin signaling. Proc. Natl Acad. Sci. USA 119, e2118220119 (2022).
Perrin, J. et al. Identifying drug targets in tissues and whole blood with thermal-shift profiling. Nat. Biotechnol. 38, 303–308 (2020).
Pazicky, S. SamPazicky/MAPX: MAP-X v1.0.0. Zenodo https://doi.org/10.5281/ZENODO.17173443 (2025).
Jackson, K. E. et al. Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II. Biochem. J. 403, 167–175 (2007).
Elzhov, T. V., Mullen, K. M., Spiess, A.-N. & Bolker, B. minpack.lm: R interface to the Levenberg–Marquardt nonlinear least-squares algorithm found in MINPACK, plus support for bounds. https://cran.r-project.org/package=minpack.lm (2023).
Harrell, F. E. Jr. Hmisc: Harrell miscellaneous. http://cran.r-project.org/web/packages/Hmisc (2024).
Liaw, A. & Wiener, M. Classification and regression by randomForest. R News 2, 18–22 (2002).
Kuhn, M. Building predictive models in R using the caret package. J. Stat. Softw. 28, 1–26 (2008).
Grau, J., Grosse, I. & Keilwagen, J. PRROC: computing and visualizing precision–recall and receiver operating characteristic curves in R. Bioinformatics 31, 2595–2597 (2015).
Moon, R. W. et al. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes. Proc. Natl Acad. Sci. USA 110, 531–536 (2013).
Cronshagen, J. et al. A system for functional studies of the major virulence factor of malaria parasites. eLife 13, RP103542 (2024).
Grüring, C. & Spielmann, T. Imaging of live malaria blood stage parasites. Methods Enzymol. 506, 81–92 (2012).
Tonkin, C. J. et al. Localization of organellar proteins in Plasmodium falciparum using a novel set of transfection vectors and a new immunofluorescence fixation method. Mol. Biochem. Parasitol. 137, 13–21 (2004).
Wickham, H. et al. Welcome to the Tidyverse. J. Open Source Softw. 4, 1686 (2019).
Gu, Z. Complex heatmap visualization. iMeta 1, e43 (2022).
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
Gustavsen, J. A., Pai, S., Isserlin, R., Demchak, B. & Pico, A. R. RCy3: network biology using Cytoscape from within R. F1000Research 8, 1774 (2019).
Schrödinger, LLC. The PyMOL molecular graphics system, version 1.8 (2015).
Pedersen, T. L. patchwork: the composer of plots (2024).
Pazicky, S. Structure of the P. falciparum exosome ring. ModelArchive https://doi.org/10.5452/ma-a867m (2025).
Pazicky, S. MAPX publication workflow. Zenodo https://doi.org/10.5281/ZENODO.17190585 (2025).
Pazicky, S. P. falciparum MAPX models, timepoints 28–40 hpi. Zenodo https://doi.org/10.5281/ZENODO.13836099 (2025).
Read more about this post…
Credits: Source
Disclaimer



Serving