{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:15:15Z","timestamp":1790154915841,"version":"4.0.1"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T00:00:00Z","timestamp":1488240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T00:00:00Z","timestamp":1488931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 GM111703"],"award-info":[{"award-number":["R01 GM111703"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["Investigators in Pathogenesis"],"award-info":[{"award-number":["Investigators in Pathogenesis"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,3,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human DJ-1 is a highly conserved and yet functionally enigmatic protein associated with a heritable form of Parkinson\u2019s disease. It has been suggested to be a redox-dependent regulatory scaffold, binding to proteins to modulate their function. Here we present the X-ray crystal structure of the\n            <jats:italic>Toxoplasma<\/jats:italic>\n            orthologue\n            <jats:italic>Toxoplasma gondii<\/jats:italic>\n            DJ-1 (TgDJ-1) at 2.1-\u00c5 resolution and show that it directly associates with calcium-dependent protein kinase 1 (CDPK1). The TgDJ-1 structure identifies an orthologously conserved arginine dyad that acts as a phospho-gatekeeper motif to control complex formation. We determined that the binding of TgDJ-1 to CDPK1 is sensitive to oxidation and calcium, and that this interaction potentiates CDPK1 kinase activity. Finally, we show that genetic deletion of TgDJ-1 results in upregulation of CDPK1 expression and that disruption of the CDPK1\/TgDJ-1 complex\n            <jats:italic>in vivo<\/jats:italic>\n            prevents normal exocytosis of parasite virulence-associated organelles called micronemes. Overall, our data suggest that TgDJ-1 functions as a noncanonical kinase-regulatory scaffold that integrates multiple intracellular signals to tune microneme exocytosis in\n            <jats:italic>T.\u00a0gondii<\/jats:italic>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Apicomplexan parasites such as\n            <jats:italic>Toxoplasma<\/jats:italic>\n            and\n            <jats:italic>Plasmodium<\/jats:italic>\n            are obligate intracellular parasites that require the protective environment of a host cell in order to replicate and survive within a host organism. These parasites secrete effector proteins from specialized apical organelles to select and invade a chosen host cell. The secretion of these organelles is a tightly regulated process coordinated by endogenous small molecules and calcium-dependent protein kinases. We previously identified the\n            <jats:italic>Toxoplasma<\/jats:italic>\n            orthologue of the highly conserved protein DJ-1 as a regulator of microneme secretion, but the molecular basis for this was not known. We have now identified the molecular mechanism for how TgDJ-1 regulates microneme secretion. TgDJ-1 interacts with the kinase responsible for the secretion of these organelles (calcium-dependent kinase 1) and synergizes with calcium to potentiate kinase activity. This interaction is direct, phosphodependent, and necessary for the normal secretion of these important organelles.\n          <\/jats:p>","DOI":"10.1128\/mbio.02189-16","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T01:10:28Z","timestamp":1488330628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Toxoplasma DJ-1 Regulates Organelle Secretion by a Direct Interaction with Calcium-Dependent Protein Kinase 1"],"prefix":"10.1128","volume":"8","author":[{"given":"Matthew A.","family":"Child","sequence":"first","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Life Sciences, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Garland","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Foe","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Madzelan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Redox Biology Center, University of Nebraska, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Treeck","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Parasitology, National Institute for Medical Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter A.","family":"van der Linden","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Oresic Bender","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eranthie","family":"Weerapana","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Redox Biology Center, University of Nebraska, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Boothroyd","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Reese","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bogyo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1133288100"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq113"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.19.6.885"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds155"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607260103"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400074"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020362"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3481"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20140051"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.40.1.617"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405511111"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-4-6"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(01)00328-0"},{"key":"e_1_3_2_15_2","first-page":"114","article-title":"Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts","volume":"73","author":"Carruthers VB","year":"1997","unstructured":"Carruthers VB Sibley LD . 1997. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol73:114\u2013123.","journal-title":"Eur J Cell Biol"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09022"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165740"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01174.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105622108"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09472"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01100a041"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(74)80110-9"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi800282d"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804243200"},{"key":"e_1_3_2_25_2","first-page":"247","article-title":"DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex","volume":"1","author":"Niki T","year":"2003","unstructured":"Niki T Takahashi-Niki K Taira T Iguchi-Ariga SM Ariga H . 2003. DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex. Mol Cancer Res1:247\u2013261.","journal-title":"Mol Cancer Res"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1795"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1104\/pp.113.222539"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.09.004"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402959101"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.85"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3130655"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004197"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.025"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085763"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806902200"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1315"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00357-08"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(97)00210-7"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5749"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61845-2"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.1999.00023.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.147934"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1626"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(03)74014-2"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909042073"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02189-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02189-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T02:37:49Z","timestamp":1646707069000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.02189-16"}},"subtitle":[],"editor":[{"given":"Jon P.","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,3,8]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,3,8]]}},"alternative-id":["10.1128\/mBio.02189-16"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02189-16","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,8]]},"assertion":[{"value":"2016-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02189-16"}}