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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,1,12]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Parasites of phylum Apicomplexa cause significant morbidity and mortality on a global scale. Central to the pathogenesis of these parasites is their ability to invade host cells through a junction formed by members of the apical membrane antigen (AMA) and rhoptry neck protein 2 (RON2) families localized to the parasite surface and host outer membrane, respectively. Here we structurally and functionally characterize\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    AMA4 (\n                    <jats:italic>Tg<\/jats:italic>\n                    AMA4), a highly divergent AMA protein. Structural analyses of\n                    <jats:italic>Tg<\/jats:italic>\n                    AMA4 in the apo and RON2\n                    <jats:sub>L1<\/jats:sub>\n                    bound forms reveal a previously underappreciated level of molecular diversity at the parasite\u2013host-cell interface that offers important insight into stage-dependent invasion strategies and yields a more comprehensive model of apicomplexan invasion.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1515898113","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T22:34:01Z","timestamp":1451342041000},"page":"398-403","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA\u2013RON2 pair"],"prefix":"10.1073","volume":"113","author":[{"given":"Michelle L.","family":"Parker","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8P 5C2, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Penarete-Vargas","sequence":"additional","affiliation":[{"name":"UMR 5235, CNRS Universit\u00e9 Montpellier, 34095 Montpellier, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phineas T.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Victoria, Victoria, BC, V8P 5C2, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"UMR 5235, CNRS Universit\u00e9 Montpellier, 34095 Montpellier, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitender P.","family":"Dubey","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705-2350;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve J.","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Victoria, Victoria, BC, V8P 5C2, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furio","family":"Spano","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanit\u00e0, Rome 00161, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryse","family":"Lebrun","sequence":"additional","affiliation":[{"name":"UMR 5235, CNRS Universit\u00e9 Montpellier, 34095 Montpellier, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Boulanger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8P 5C2, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,12,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/CMR.05013-11","article-title":"Epidemiology of and diagnostic strategies for toxoplasmosis","volume":"25","author":"Robert-Gangneux F","year":"2012","unstructured":"F Robert-Gangneux, ML Dard\u00e9, Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 25, 264\u2013296 (2012).","journal-title":"Clin Microbiol Rev"},{"key":"e_1_3_4_2_2","volume-title":"World Malaria Report","author":"World Health Organization","year":"2014","unstructured":"; World Health Organization World Malaria Report (World Health Organization, Geneva, 2014)."},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.mib.2013.07.004","article-title":"Key molecular events during host cell invasion by Apicomplexan pathogens","volume":"16","author":"Sharma P","year":"2013","unstructured":"P Sharma, CE Chitnis, Key molecular events during host cell invasion by Apicomplexan pathogens. Curr Opin Microbiol 16, 432\u2013437 (2013).","journal-title":"Curr Opin Microbiol"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1083\/jcb.77.1.72","article-title":"Erythrocyte entry by malarial parasites. 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Trends Parasitol 24, 509\u2013516 (2008).","journal-title":"Trends Parasitol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/oxfordjournals.molbev.a004171","article-title":"Evolutionary relationships of conserved cysteine-rich motifs in adhesive molecules of malaria parasites","volume":"19","author":"Michon P","year":"2002","unstructured":"P Michon, JR Stevens, O Kaneko, JH Adams, Evolutionary relationships of conserved cysteine-rich motifs in adhesive molecules of malaria parasites. Mol Biol Evol 19, 1128\u20131142 (2002).","journal-title":"Mol Biol Evol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.molbiopara.2005.05.003","article-title":"Apical expression of three RhopH1\/Clag proteins as components of the Plasmodium falciparum RhopH complex","volume":"143","author":"Kaneko O","year":"2005","unstructured":"O Kaneko, , Apical expression of three RhopH1\/Clag proteins as components of the Plasmodium falciparum RhopH complex. Mol Biochem Parasitol 143, 20\u201328 (2005).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2011.05.002","article-title":"Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells","volume":"145","author":"Nguitragool W","year":"2011","unstructured":"W Nguitragool, , Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells. Cell 145, 665\u2013677 (2011).","journal-title":"Cell"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"15644","DOI":"10.1074\/jbc.M109.092619","article-title":"Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii","volume":"285","author":"Crawford J","year":"2010","unstructured":"J Crawford, ML Tonkin, O Grujic, MJ Boulanger, Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii. J Biol Chem 285, 15644\u201315652 (2010).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/pro.2193","article-title":"Babesia divergens and Neospora caninum apical membrane antigen 1 structures reveal selectivity and plasticity in apicomplexan parasite host cell invasion","volume":"22","author":"Tonkin ML","year":"2013","unstructured":"ML Tonkin, J Crawford, ML Lebrun, MJ Boulanger, Babesia divergens and Neospora caninum apical membrane antigen 1 structures reveal selectivity and plasticity in apicomplexan parasite host cell invasion. Protein Sci 22, 114\u2013127 (2013).","journal-title":"Protein Sci"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"e0126206","DOI":"10.1371\/journal.pone.0126206","article-title":"An extended surface loop on Toxoplasma gondii apical membrane antigen 1 (AMA1) governs ligand binding selectivity","volume":"10","author":"Parker ML","year":"2015","unstructured":"ML Parker, MJ Boulanger, An extended surface loop on Toxoplasma gondii apical membrane antigen 1 (AMA1) governs ligand binding selectivity. PLoS One 10, e0126206 (2015).","journal-title":"PLoS One"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"e1004539","DOI":"10.1371\/journal.ppat.1004539","article-title":"The shear stress of host cell invasion: Exploring the role of biomolecular complexes","volume":"11","author":"Tonkin ML","year":"2015","unstructured":"ML Tonkin, MJ Boulanger, The shear stress of host cell invasion: Exploring the role of biomolecular complexes. 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Proc Natl Acad Sci USA 102, 12736\u201312741 (2005).","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1515898113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1515898113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T10:15:17Z","timestamp":1654596917000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1515898113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,28]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,1,12]]}},"alternative-id":["10.1073\/pnas.1515898113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1515898113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,28]]},"assertion":[{"value":"2015-12-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}