{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:34:00Z","timestamp":1787884440427,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.pbio.3003520","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1182369"],"award-info":[{"award-number":["GNT1182369"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP230100853"],"award-info":[{"award-number":["DP230100853"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Government Research Training Program"},{"name":"Gwendolyn Woodroofe PhD scholarship, Australian National University"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    The assembly of iron\u2013sulfur (FeS) clusters for cytosolic and nuclear proteins is essential for eukaryotic cell biology. This assembly is mediated by the Cytosolic Iron\u2013sulfur Assembly (CIA) pathway, which localizes to the cytosol of most eukaryotes. We showed previously that the scaffold protein on which cytosolic FeS clusters assemble localizes to the mitochondrion of the apicomplexan parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    . The localization and importance of the remainder of the pathway in these parasites, however, remained unclear. Here, we undertake a comprehensive analysis of the CIA pathway in\n                    <jats:italic>T. gondii<\/jats:italic>\n                    parasites. We present evidence that the CIA pathway localizes predominantly to the mitochondrion of the parasite and is essential for parasite survival. We show that the three proteins that make up the CIA Targeting Complex (CTC), which facilitates the transfer of FeS clusters to cytosolic and nuclear client proteins, exhibit dual localization to the mitochondrion and cytosol. We reveal that mitochondrial targeting of the CTC is mediated by a novel loop on the CIA1 protein of the complex, and that this loop is critical for parasite survival. We show that an aromatic amino acid motif in the loop facilitates mitochondrial targeting, and that this loop is functionally conserved in apicomplexans and their closest free-living relatives. Our study provides a comprehensive analysis of the CIA pathway in an important group of intracellular parasites, and elucidates pivotal differences in an otherwise ancient and highly conserved biosynthetic pathway that may reflect an evolutionary fitness advantage conferred on\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    and related organisms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003520","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T18:37:26Z","timestamp":1764095846000},"page":"e3003520","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel targeting domain directs essential components of the cytosolic iron\u2013sulfur cluster assembly pathway to the mitochondrion of Toxoplasma parasites"],"prefix":"10.1371","volume":"23","author":[{"given":"Evie R.","family":"Hodgson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenni A.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadzai Victor","family":"Makota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-9821","authenticated-orcid":true,"given":"Giel G.","family":"van Dooren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"6","key":"pbio.3003520.ref001","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.bbamcr.2015.03.001","article-title":"Special issue on iron-sulfur proteins: structure, function, biogenesis and diseases","volume":"1853","author":"R Lill","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"pbio.3003520.ref002","doi-asserted-by":"crossref","first-page":"214229","DOI":"10.1016\/j.ccr.2021.214229","article-title":"The expanding utility of iron-sulfur clusters: their functional roles in biology, synthetic small molecules, maquettes and artificial proteins, biomimetic materials, and therapeutic strategies","volume":"453","author":"AE Boncella","year":"2022","journal-title":"Coord Chem Rev"},{"key":"pbio.3003520.ref003","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.3389\/fmicb.2019.02478","article-title":"On the origin of iron\/sulfur cluster biosynthesis in eukaryotes","volume":"10","author":"AD Tsaousis","year":"2019","journal-title":"Front Microbiol"},{"issue":"1","key":"pbio.3003520.ref004","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1038\/s41467-022-32006-8","article-title":"Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria","volume":"13","author":"P Li","year":"2022","journal-title":"Nat Commun"},{"key":"pbio.3003520.ref005","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1515\/hsz-2020-0117","article-title":"From the discovery to molecular understanding of cellular iron-sulfur protein biogenesis","volume":"401","author":"R Lill","year":"2020","journal-title":"Biol Chem"},{"issue":"5","key":"pbio.3003520.ref006","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nchembio872","article-title":"The Cfd1-Nbp35 complex acts as a scaffold for iron-sulfur protein assembly in the yeast cytosol","volume":"3","author":"DJA Netz","year":"2007","journal-title":"Nat Chem Biol"},{"issue":"39","key":"pbio.3003520.ref007","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1807762115","article-title":"Function and crystal structure of the dimeric P-loop ATPase CFD1 coordinating an exposed [4Fe-4S] cluster for transfer to apoproteins","volume":"115","author":"O Stehling","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"pbio.3003520.ref008","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1038\/sj.emboj.7600216","article-title":"The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron-sulphur proteins","volume":"23","author":"J Balk","year":"2004","journal-title":"EMBO J"},{"issue":"6091","key":"pbio.3003520.ref009","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1126\/science.1219664","article-title":"MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism","volume":"337","author":"K Gari","year":"2012","journal-title":"Science"},{"issue":"8","key":"pbio.3003520.ref010","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/s41594-020-0454-0","article-title":"Structural insights into Fe-S protein biogenesis by the CIA targeting complex","volume":"27","author":"SA Kassube","year":"2020","journal-title":"Nat Struct Mol Biol"},{"issue":"6091","key":"pbio.3003520.ref011","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1126\/science.1219723","article-title":"MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity","volume":"337","author":"O Stehling","year":"2012","journal-title":"Science"},{"issue":"6","key":"pbio.3003520.ref012","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.celrep.2017.01.037","article-title":"The CIA targeting complex is highly regulated and provides two distinct binding sites for client iron-sulfur proteins","volume":"18","author":"DC Odermatt","year":"2017","journal-title":"Cell Rep"},{"issue":"3","key":"pbio.3003520.ref013","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ejop.2004.01.002","article-title":"Protalveolate phylogeny and systematics and the origins of Sporozoa and dinoflagellates (phylum Myzozoa nom. nov.)","volume":"40","author":"T Cavalier-Smith","year":"2004","journal-title":"Eur J Protistol"},{"issue":"4","key":"pbio.3003520.ref014","doi-asserted-by":"crossref","DOI":"10.1128\/mmbr.00197-22","article-title":"Adaptations and metabolic evolution of myzozoan protists across diverse lifestyles and environments","volume":"88","author":"RF Waller","year":"2024","journal-title":"Microbiol Mol Biol Rev"},{"issue":"5","key":"pbio.3003520.ref015","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1111\/mmi.14651","article-title":"A key cytosolic iron-sulfur cluster synthesis protein localizes to the mitochondrion of Toxoplasma gondii","volume":"115","author":"YTV Aw","year":"2021","journal-title":"Mol Microbiol"},{"issue":"1","key":"pbio.3003520.ref016","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12862-021-01777-x","article-title":"The iron-sulfur scaffold protein HCF101 unveils the complexity of organellar evolution in SAR, Haptista and Cryptista","volume":"21","author":"J Pyrih","year":"2021","journal-title":"BMC Ecol Evol"},{"key":"pbio.3003520.ref017","article-title":"ToxoDB: an integrated Toxoplasma gondii database resource","volume":"36","author":"B Gajria","year":"2008","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pbio.3003520.ref018","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009797","article-title":"A novel heteromeric pantothenate kinase complex in apicomplexan parasites","volume":"17","author":"ET Tjhin","year":"2021","journal-title":"PLoS Pathog"},{"issue":"4","key":"pbio.3003520.ref019","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.2728","article-title":"Conditional knockdown of proteins using auxin-inducible degron (AID) fusions in Toxoplasma gondii","volume":"8","author":"KM Brown","year":"2018","journal-title":"Bio Protoc"},{"issue":"2","key":"pbio.3003520.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3003028","article-title":"The HCF101 protein is an important component of the cytosolic iron-sulfur synthesis pathway in Toxoplasma gondii","volume":"23","author":"EA Renaud","year":"2025","journal-title":"PLoS Biol"},{"issue":"10","key":"pbio.3003520.ref021","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00872-24","article-title":"The Toxoplasma gondii mitochondrial transporter ABCB7L is essential for the biogenesis of cytosolic and nuclear iron-sulfur cluster proteins and cytosolic translation","volume":"15","author":"AE Maclean","year":"2024","journal-title":"mBio"},{"issue":"9","key":"pbio.3003520.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012593","article-title":"ATM1, an essential conserved transporter in Apicomplexa, bridges mitochondrial and cytosolic [Fe-S] biogenesis","volume":"20","author":"D Shrivastava","year":"2024","journal-title":"PLoS Pathog"},{"issue":"9","key":"pbio.3003520.ref023","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.bbagen.2018.05.019","article-title":"Investigating the role of the human CIA2A-CIAO1 complex in the maturation of aconitase","volume":"1862","author":"V Maione","year":"2018","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"7325","key":"pbio.3003520.ref024","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nature09472","article-title":"Quantitative reactivity profiling predicts functional cysteines in proteomes","volume":"468","author":"E Weerapana","year":"2010","journal-title":"Nature"},{"issue":"44","key":"pbio.3003520.ref025","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2311057120","article-title":"Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide","volume":"120","author":"MD Marquez","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"pbio.3003520.ref026","doi-asserted-by":"crossref","first-page":"10833","DOI":"10.1128\/MCB.25.24.10833-10841.2005","article-title":"The essential WD40 protein Cia1 is involved in a late step of cytosolic and nuclear iron-sulfur protein assembly","volume":"25","author":"J Balk","year":"2005","journal-title":"Mol Cell Biol"},{"issue":"3","key":"pbio.3003520.ref027","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s13238-011-1018-1","article-title":"Structure and function of WD40 domain proteins","volume":"2","author":"C Xu","year":"2011","journal-title":"Protein Cell"},{"issue":"10","key":"pbio.3003520.ref028","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.str.2007.08.009","article-title":"Structure of the yeast WD40 domain protein Cia1, a component acting late in iron-sulfur protein biogenesis","volume":"15","author":"V Srinivasan","year":"2007","journal-title":"Structure"},{"key":"pbio.3003520.ref029","doi-asserted-by":"crossref","first-page":"42746","DOI":"10.1038\/srep42746","article-title":"Mitochondrial behaviour throughout the lytic cycle of Toxoplasma gondii","volume":"7","author":"J Ovciarikova","year":"2017","journal-title":"Sci Rep"},{"issue":"6","key":"pbio.3003520.ref030","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nmeth.3365","article-title":"High-performance probes for light and electron microscopy","volume":"12","author":"S Viswanathan","year":"2015","journal-title":"Nat Methods"},{"issue":"3","key":"pbio.3003520.ref031","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/tra.12464","article-title":"Targeting of tail-anchored membrane proteins to subcellular organelles in Toxoplasma gondii","volume":"18","author":"LR Padgett","year":"2017","journal-title":"Traffic"},{"issue":"7","key":"pbio.3003520.ref032","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2121491119","article-title":"A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics","volume":"119","author":"O Karmi","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pbio.3003520.ref033","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2020.09.011","article-title":"A comprehensive subcellular atlas of the Toxoplasma proteome via hyperLOPIT provides spatial context for protein functions","volume":"28","author":"K Barylyuk","year":"2020","journal-title":"Cell Host Microbe"},{"issue":"20","key":"pbio.3003520.ref034","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.255299","article-title":"Depletion of a Toxoplasma porin leads to defects in mitochondrial morphology and contacts with the endoplasmic reticulum","volume":"134","author":"N Mallo","year":"2021","journal-title":"J Cell Sci"},{"issue":"10","key":"pbio.3003520.ref035","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nchembio.432","article-title":"Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis","volume":"6","author":"DJA Netz","year":"2010","journal-title":"Nat Chem Biol"},{"issue":"18","key":"pbio.3003520.ref036","doi-asserted-by":"crossref","first-page":"5569","DOI":"10.1128\/MCB.00642-08","article-title":"Dre2, a conserved eukaryotic Fe\/S cluster protein, functions in cytosolic Fe\/S protein biogenesis","volume":"28","author":"Y Zhang","year":"2008","journal-title":"Mol Cell Biol"},{"issue":"3","key":"pbio.3003520.ref037","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00775-020-01778-z","article-title":"CIAO3 protein forms a stable ternary complex with two key players of the human cytosolic iron-sulfur cluster assembly machinery","volume":"25","author":"V Maione","year":"2020","journal-title":"J Biol Inorg Chem"},{"issue":"1","key":"pbio.3003520.ref038","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13321-020-00437-4","article-title":"Aromatic clusters in protein-protein and protein-drug complexes","volume":"12","author":"E Lanzarotti","year":"2020","journal-title":"J Cheminform"},{"issue":"24","key":"pbio.3003520.ref039","doi-asserted-by":"crossref","first-page":"21459","DOI":"10.1074\/jbc.M301652200","article-title":"Binding of peptides with basic and aromatic residues to bilayer membranes: phenylalanine in the myristoylated alanine-rich C kinase substrate effector domain penetrates into the hydrophobic core of the bilayer","volume":"278","author":"W Zhang","year":"2003","journal-title":"J Biol Chem"},{"issue":"35","key":"pbio.3003520.ref040","doi-asserted-by":"crossref","first-page":"25318","DOI":"10.1074\/jbc.M113.491373","article-title":"Elongator protein 3 (Elp3) lysine acetyltransferase is a tail-anchored mitochondrial protein in Toxoplasma gondii","volume":"288","author":"KL Stilger","year":"2013","journal-title":"J Biol Chem"},{"issue":"1","key":"pbio.3003520.ref041","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0189688","article-title":"Elp3 and RlmN: a tale of two mitochondrial tail-anchored radical SAM enzymes in Toxoplasma gondii","volume":"13","author":"LR Padgett","year":"2018","journal-title":"PLoS One"},{"issue":"6","key":"pbio.3003520.ref042","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2016.08.019","article-title":"A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes","volume":"166","author":"SM Sidik","year":"2016","journal-title":"Cell"},{"issue":"12","key":"pbio.3003520.ref043","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3390\/inorganics12120316","article-title":"Guardians of the genome: iron\u2013sulfur proteins in the nucleus","volume":"12","author":"L Novoa-Aponte","year":"2024","journal-title":"Inorganics"},{"issue":"9","key":"pbio.3003520.ref044","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.3390\/ijms21093395","article-title":"Regulation of iron homeostasis and use in chloroplasts","volume":"21","author":"GE Kroh","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"5812","key":"pbio.3003520.ref045","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.1131669","article-title":"Mesoscale iron enrichment experiments 1993-2005: synthesis and future directions","volume":"315","author":"PW Boyd","year":"2007","journal-title":"Science"},{"issue":"1","key":"pbio.3003520.ref046","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/s41467-021-21339-5","article-title":"Massive Southern Ocean phytoplankton bloom fed by iron of possible hydrothermal origin","volume":"12","author":"CMS Schine","year":"2021","journal-title":"Nat Commun"},{"issue":"14","key":"pbio.3003520.ref047","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1093\/emboj\/18.14.3981","article-title":"The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe\/S proteins","volume":"18","author":"G Kispal","year":"1999","journal-title":"EMBO J"},{"issue":"3","key":"pbio.3003520.ref048","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01114-14","article-title":"Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR\/CAS9","volume":"5","author":"B Shen","year":"2014","journal-title":"mBio"},{"issue":"2","key":"pbio.3003520.ref049","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009211","article-title":"Divergent features of the coenzyme Q:cytochrome c oxidoreductase complex in Toxoplasma gondii parasites","volume":"17","author":"JA Hayward","year":"2021","journal-title":"PLoS Pathog"},{"key":"pbio.3003520.ref050","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/B978-0-12-815041-2.00020-7","article-title":"Genetic manipulation of Toxoplasma gondii.","volume-title":"Toxoplasma gondii: the model apicomplexan","author":"D Jacot","year":"2020","edition":"3"},{"issue":"2","key":"pbio.3003520.ref051","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0166-6851(96)02598-4","article-title":"A novel epitope tag system to study protein targeting and organelle biogenesis in Trypanosoma brucei","volume":"77","author":"P Bastin","year":"1996","journal-title":"Mol Biochem Parasitol"},{"issue":"37","key":"pbio.3003520.ref052","doi-asserted-by":"crossref","first-page":"19335","DOI":"10.1074\/jbc.M116.725069","article-title":"The import of proteins into the mitochondrion of Toxoplasma gondii","volume":"291","author":"GG van Dooren","year":"2016","journal-title":"J Biol Chem"},{"issue":"7","key":"pbio.3003520.ref053","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"7","key":"pbio.3003520.ref054","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"pbio.3003520.ref055","doi-asserted-by":"crossref","first-page":"14455","DOI":"10.1038\/ncomms14455","article-title":"Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites","volume":"8","author":"E Rajendran","year":"2017","journal-title":"Nat Commun"},{"key":"pbio.3003520.ref056","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkj123","article-title":"OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups","volume":"34","author":"F Chen","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"17","key":"pbio.3003520.ref057","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"SF Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003520.ref058","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: the universal protein knowledgebase in 2023","volume":"51","author":"Consortium UniProt","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003520.ref059","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae241","article-title":"The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024","volume":"52","author":"F Madeira","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003520.ref060","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkad1003","article-title":"VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center in 2023","volume":"52","author":"J Alvarez-Jarreta","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pbio.3003520.ref061","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014a multiple sequence alignment editor and analysis workbench","volume":"25","author":"AM Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"issue":"7873","key":"pbio.3003520.ref062","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"issue":"15","key":"pbio.3003520.ref063","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.jmb.2018.01.013","article-title":"EzMol: a web server wizard for the rapid visualization and image production of protein and nucleic acid structures","volume":"430","author":"CR Reynolds","year":"2018","journal-title":"J Mol Biol"},{"issue":"1","key":"pbio.3003520.ref064","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tree.2019.08.008","article-title":"The new tree of eukaryotes","volume":"35","author":"F Burki","year":"2020","journal-title":"Trends Ecol Evol"},{"issue":"13","key":"pbio.3003520.ref065","doi-asserted-by":"crossref","DOI":"10.1016\/j.cub.2021.04.028","article-title":"Parallel functional reduction in the mitochondria of apicomplexan parasites","volume":"31","author":"V Mathur","year":"2021","journal-title":"Curr Biol"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3003520","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003520","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:44:27Z","timestamp":1764787467000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003520"}},"subtitle":[],"editor":[{"given":"Gary E","family":"Ward","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003520","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]}}}