{"id":9302,"date":"2018-09-19T09:41:45","date_gmt":"2018-09-19T13:41:45","guid":{"rendered":"https:\/\/biology.mit.edu\/?p=9302"},"modified":"2018-09-19T09:42:02","modified_gmt":"2018-09-19T13:42:02","slug":"parasites-riff-on-essential-enzyme-highlights-unique-biology","status":"publish","type":"post","link":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/","title":{"rendered":"Parasite\u2019s riff on essential enzyme highlights unique biology"},"content":{"rendered":"<p dir=\"ltr\">Cambridge, Mass. &#8212; The primary currency of energy in cells\u2014adenosine triphosphate (ATP)\u2014is essential for their survival and without it, cellular processes would seize. In the apicomplexan\u00a0<em>Toxoplasma gondii\u00a0<\/em>(<em>T. gondii<\/em>), a parasite that Whitehead Member\u00a0<a href=\"http:\/\/wi.mit.edu\/people\/faculty\/lourido\" target=\"_blank\" rel=\"noopener\">Sebastian Lourido<\/a>\u00a0studies, key components of the ATP synthase\u2014the enzyme responsible for ATP production\u2014have remained elusive. While investigating indispensable proteins with unknown functions, Lourido and Diego Huet, a postdoctoral researcher in Lourido\u2019s lab, identified a critical component of the enzyme. While highly conserved from yeast to humans, it proved to be considerably different in\u00a0<em>T. gondii<\/em>. The findings, published online September 11 in the journal\u00a0<em>eLife<\/em>, underscore the unique biology of these parasites and highlight differences between them and their human hosts.<\/p>\n<p dir=\"ltr\">More closely related to plants than to animals, the single-celled apicomplexans are among the most common and deadly human pathogens. According to the World Health Organization, every year these diseases sicken hundreds of millions, kill hundreds of thousands\u2014primarily children\u2014and cost billions of dollars to treat. Species of apicomplexans cause malaria (<em>Plasmodium<\/em>\u00a0spp.), cryptosporidiosis (<em>Cryptosporidium<\/em>\u00a0spp.), and toxoplasmosis (T. gondii).<\/p>\n<p dir=\"ltr\">Using a CRISPR-based genetic screen that they had adapted to\u00a0<em>T. gondii<\/em>, Lourido and Huet had previously identified about 200 genes in\u00a0<em>T. gondii<\/em>\u00a0that are fitness-conferring and specific to apicomplexans. Of that cadre, a few were localized to the mitochondria, where cells manufacture ATP, the cellular currency of energy. Because those genes have not been annotated previously, and the proteins encoded by them have no known function, Huet ran their protein sequences through a database that compared them to protein sequences with known structures.<\/p>\n<p dir=\"ltr\">One of the proteins came back with an interesting hit: it shares structural similarity, but not sequence similarity, with an integral part of the ATP synthase. Most of the protein subunits that compose the apicomplexan ATP synthase have been identified, but key components of the stator\u2014a portion of the enzyme essential for its function\u2014was not yet known.<\/p>\n<p dir=\"ltr\">When Huet experimentally removed the function of the stator subunit in\u00a0<em>T. gondii<\/em>, the parasites\u2019 growth stalled, their mitochondria were misshapen and shrunken, and energy production halted\u2014all traits typical of interrupted ATP synthase function.<\/p>\n<p dir=\"ltr\">Because the apicomplexan ATP synthase varies so much from its hosts\u2019 version, those differences, like the unusual stator, could serve as future drug targets. But for Lourido, who is also an assistant professor of biology at Massachusetts Institute of Technology (MIT), the unique stator protein emphasizes how unique and extraordinary apicomplexan organisms are compared to us and their other hosts.<\/p>\n<p dir=\"ltr\">This work was supported by the National Institutes of Health (NIH grants 1DP5OD017892, R21AI123746, and K99AI137218).<\/p>\n<p dir=\"ltr\">* * *<\/p>\n<h4 dir=\"ltr\">Sebastian Lourido\u2019s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also an assistant professor of biology at Massachusetts Institute of Technology.<\/h4>\n<h4 dir=\"ltr\">* * *<\/h4>\n<h4 dir=\"ltr\">Full Citation:<\/h4>\n<h4 dir=\"ltr\">\u201cIdentification of cryptic subunits from an apicomplexan ATP synthase\u201d<\/h4>\n<h4 dir=\"ltr\"><em>eLife<\/em>, online September 11, 2018. \u00a0DOI: 10.7554\/eLife.38097<\/h4>\n<h4 dir=\"ltr\">Diego Huet (1) , Esther Rajendran (2) , Giel G van Dooren (2) , Sebastian Lourido (1,3*).<\/h4>\n<h4 dir=\"ltr\">1. Whitehead Institute for Biomedical Research, Cambridge, United States<\/h4>\n<h4 dir=\"ltr\">2. Research School of Biology, Australian National University, Canberra, Australia<\/h4>\n<h4 dir=\"ltr\">3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States<\/h4>\n","protected":false},"excerpt":{"rendered":"<p>Cambridge, Mass. &#8212; The primary currency of energy in cells\u2014adenosine triphosphate (ATP)\u2014is essential for their survival and without it, cellular processes would seize. In the apicomplexan\u00a0Toxoplasma gondii\u00a0(T. gondii), a parasite that Whitehead Member\u00a0Sebastian Lourido\u00a0studies, key components of the ATP synthase\u2014the enzyme responsible for ATP production\u2014have remained elusive. While investigating indispensable proteins with unknown functions, Lourido [&hellip;]<\/p>\n","protected":false},"author":16,"featured_media":9303,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-9302","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","placement-placement-homepage","research-area-cell-biology","research-area-human-disease","research-area-microbiology"],"acf":[],"yoast_head":"\n<title>Parasite\u2019s riff on essential enzyme highlights unique biology - MIT Department of Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Parasite\u2019s riff on essential enzyme highlights unique biology\" \/>\n<meta property=\"og:description\" content=\"Cambridge, Mass. &#8212; The primary currency of energy in cells\u2014adenosine triphosphate (ATP)\u2014is essential for their survival and without it, cellular processes would seize. In the apicomplexan\u00a0Toxoplasma gondii\u00a0(T. gondii), a parasite that Whitehead Member\u00a0Sebastian Lourido\u00a0studies, key components of the ATP synthase\u2014the enzyme responsible for ATP production\u2014have remained elusive. While investigating indispensable proteins with unknown functions, Lourido [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/\" \/>\n<meta property=\"og:site_name\" content=\"MIT Department of Biology\" \/>\n<meta property=\"article:published_time\" content=\"2018-09-19T13:41:45+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2018-09-19T13:42:02+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1134\" \/>\n\t<meta property=\"og:image:height\" content=\"760\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Raleigh McElvery\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Raleigh McElvery\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/\",\"url\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/\",\"name\":\"Parasite\u2019s riff on essential enzyme highlights unique biology - MIT Department of Biology\",\"isPartOf\":{\"@id\":\"https:\/\/biology.mit.edu\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg\",\"datePublished\":\"2018-09-19T13:41:45+00:00\",\"dateModified\":\"2018-09-19T13:42:02+00:00\",\"author\":{\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66\"},\"breadcrumb\":{\"@id\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#primaryimage\",\"url\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg\",\"contentUrl\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg\",\"width\":1134,\"height\":760,\"caption\":\"Colorful blobs\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\/\/biology.mit.edu\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Parasite\u2019s riff on essential enzyme highlights unique biology\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/biology.mit.edu\/#website\",\"url\":\"https:\/\/biology.mit.edu\/\",\"name\":\"MIT Department of Biology\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/biology.mit.edu\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66\",\"name\":\"Raleigh McElvery\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/image\/\",\"url\":\"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g\",\"contentUrl\":\"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g\",\"caption\":\"Raleigh McElvery\"},\"url\":\"https:\/\/biology.mit.edu\/author\/rmcelvery\/\"}]}<\/script>\n","yoast_head_json":{"title":"Parasite\u2019s riff on essential enzyme highlights unique biology - MIT Department of Biology","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/","og_locale":"en_US","og_type":"article","og_title":"Parasite\u2019s riff on essential enzyme highlights unique biology","og_description":"Cambridge, Mass. &#8212; The primary currency of energy in cells\u2014adenosine triphosphate (ATP)\u2014is essential for their survival and without it, cellular processes would seize. In the apicomplexan\u00a0Toxoplasma gondii\u00a0(T. gondii), a parasite that Whitehead Member\u00a0Sebastian Lourido\u00a0studies, key components of the ATP synthase\u2014the enzyme responsible for ATP production\u2014have remained elusive. While investigating indispensable proteins with unknown functions, Lourido [&hellip;]","og_url":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/","og_site_name":"MIT Department of Biology","article_published_time":"2018-09-19T13:41:45+00:00","article_modified_time":"2018-09-19T13:42:02+00:00","og_image":[{"width":1134,"height":760,"url":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg","type":"image\/jpeg"}],"author":"Raleigh McElvery","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Raleigh McElvery","Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/","url":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/","name":"Parasite\u2019s riff on essential enzyme highlights unique biology - MIT Department of Biology","isPartOf":{"@id":"https:\/\/biology.mit.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#primaryimage"},"image":{"@id":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#primaryimage"},"thumbnailUrl":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg","datePublished":"2018-09-19T13:41:45+00:00","dateModified":"2018-09-19T13:42:02+00:00","author":{"@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66"},"breadcrumb":{"@id":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/"]}]},{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#primaryimage","url":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg","contentUrl":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2018\/09\/Lourido_Paper.jpg","width":1134,"height":760,"caption":"Colorful blobs"},{"@type":"BreadcrumbList","@id":"https:\/\/biology.mit.edu\/parasites-riff-on-essential-enzyme-highlights-unique-biology\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/biology.mit.edu\/"},{"@type":"ListItem","position":2,"name":"Parasite\u2019s riff on essential enzyme highlights unique biology"}]},{"@type":"WebSite","@id":"https:\/\/biology.mit.edu\/#website","url":"https:\/\/biology.mit.edu\/","name":"MIT Department of Biology","description":"","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/biology.mit.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66","name":"Raleigh McElvery","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/image\/","url":"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g","caption":"Raleigh McElvery"},"url":"https:\/\/biology.mit.edu\/author\/rmcelvery\/"}]}},"_links":{"self":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/9302"}],"collection":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/comments?post=9302"}],"version-history":[{"count":2,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/9302\/revisions"}],"predecessor-version":[{"id":9305,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/9302\/revisions\/9305"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/media\/9303"}],"wp:attachment":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/media?parent=9302"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/categories?post=9302"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/tags?post=9302"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}