{"id":6443,"date":"2016-01-15T15:19:15","date_gmt":"2016-01-15T14:19:15","guid":{"rendered":"http:\/\/news.embl.de\/?p=6443"},"modified":"2024-03-25T10:34:13","modified_gmt":"2024-03-25T09:34:13","slug":"1601-endolysin","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/","title":{"rendered":"One gene, two proteins, one complex"},"content":{"rendered":"\n<p>In a study recently published in the <em>Journal of Biological Chemistry<\/em>, Meijers and collaborators from the Institute of Food Research in Norwich, UK, show that the genes of viral enzymes that degrade the cell walls of <em>Clostridia<\/em>&nbsp;bacteria produce not the usual one, but two proteins. The results give insights into how these enzymes degrade the bacterial cell wall, and could be used to combat a range of <em>Clostridium<\/em>&nbsp;infections.<\/p>\n\n\n\n<p>Dotted along the seemingly infinite string of A, T, G and C that make up an organism\u2019s DNA, specific triplets of these letters \u2013 known as \u2018codons\u2019 \u2013 indicate where the cell\u2019s machinery should start, and stop, when it translates the language of genes into proteins. Some genes have not one, but several start codons, resulting in proteins of different lengths being produced from one gene. \u201cThis study shows how two such proteins from the same gene form a complex, and how the shorter protein regulates the full length protein,\u201d says Meijers, \u201cto our knowledge that has never been seen before.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Coming of phage<\/h2>\n\n\n\n<p>The double-packed gene studied by Meijers belongs to a virus that preys on species of <em>Clostridia<\/em> bacteria. After infecting their target, these viruses \u2013 or bacteriophages \u2013 break open the bacterial cell wall using enzymes known as endolysins, thereby destroying the bacterial cells. \u201cIt\u2019s a perfectly timed process,\u201d says Meijers, who is interested in understanding how these enzymes work. \u201cAt a fixed time point after infection, when all resources in the bacteria cell have been exhausted and the viral progeny are ready to be released, the endolysins start to break open the cell wall.\u201d But just what triggers the endolysin to start its work is not yet understood.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>Bacteriophages, and particularly their cell-wall degrading enzymes, are very interesting research objects.<\/p><\/blockquote>\n\n\n\n<p>With their precise choice of target, bacteriophages have long been considered potential allies in the fight against persistent bacterial infections. \u201cIn an era when many bacteria have evolved mechanisms to make them resistant to treatments such as antibiotics, we urgently need alternative ways of combatting bacterial infections,\u201d explains Meijers. \u201cSince they naturally destroy specific bacteria, bacteriophages, and particularly their cell-wall degrading enzymes, are very interesting research objects. How do they do it, and what can we learn from them?\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">A cheesy problem<\/h2>\n\n\n\n<p>Of the approximately 100 species of&nbsp;<em>Clostridium<\/em>, a handful play a disruptive role in human society. Meijers and collaborators focused on <em>C. tyrobutyricum,<\/em> the byproducts of which in raw milk represent a significant economic drain for the cheese making industry. This study presents the 3D atomic structure of the complete <em>C. tyrobutyricum<\/em> endolysin bound to a smaller protein called Cell-wall Bound Domain, or CBD \u2013 the structure of which was <a href=\"http:\/\/news.embl.de\/science\/1407_cdiff\/\">solved by the group in 2014<\/a>. \u201cThese two proteins are both coded for by the same gene,\u201d says Meijers. Reading and translating the full-length gene produces the endolysin; reading from the second start codon produces the small CBD molecule.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>It seems the bacteriophage uses both proteins to regulate the activity of the endolysin.<\/p><\/blockquote>\n\n\n\n<p>&#8220;It seems the bacteriophage uses both proteins to regulate the activity of the endolysin,\u201d says Meijers. By removing the second start codon from the gene, the group shows that the activity of the endolysin is greatly reduced. Too much CBD, however, and activity is also slowed. These findings build on earlier work: \u201cWe originally thought that it was the endolysin complex that initiated and activated the bacteria cell wall break-up,\u201d Meijers adds, \u201cBut actually it seems the activation of the endolysin begins in the gene itself.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">The long and short of it<\/h2>\n\n\n\n<p>After inserting the endolysin gene into milk bacteria used in cheese making, the researchers could show that both the full endolysin enzyme and the smaller CBD were produced by the new host. \u201cWe tricked the milk bacteria into producing the endolysin and the CBD for us, but these proteins remain trapped inside the bacterial cell,\u201d explains Meijers. \u201cWe have made the full-length endolysin pass across the cell wall, but so far not the shorter CBD \u2013 without both parts, no complex forms and activity is reduced.\u201d This highlights again how important both parts are, and presents a potential path for future molecule design for treating <em>Clostridia<\/em> infections. Meijers concludes: \u201cCheese makers currently add large amounts of enzymes to the cheese to combat the effects of the <em>Clostridia&nbsp;\u2013 <\/em>maybe in future we can just use small amounts of modified milk bacteria that will effectively destroy any <em>Clostridia<\/em> present.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Further insights into how viral enzymes degrade the cell walls of Clostridia bacteria.<\/p>\n","protected":false},"author":18,"featured_media":6457,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[29,53,32,100,35],"embl_taxonomy":[],"class_list":["post-6443","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-crystallography","tag-hamburg","tag-health","tag-meijers","tag-structural-biology"],"acf":{"article_intro":"<p>&#8220;To see two proteins produced from the same gene that then bind together to form a complex \u2013 that is truly unique!\u201d says EMBL Hamburg group leader <a href=\"http:\/\/www.embl-hamburg.de\/research\/unit\/meijers\/\">Rob Meijers <\/a>excitedly.<\/p>\n","related_links":[{"link_description":"Institute of Food Research in Norwich, UK","link_url":"http:\/\/www.ifr.ac.uk\/"},{"link_description":"Meijers and colleagues show how bacteriophages destroy Clostridium difficile cells \u2013 Fighting bacteria, EMBLetc. 24 July 2014","link_url":"http:\/\/news.embl.de\/science\/1407_cdiff\/"}],"article_sources":[{"source_description":"<p>Dunne M\u00a0<em>et al.\u00a0<em>Journal of Biological Chemistry<\/em><\/em>, 18 December 2015. DOI:\u00a010.1074\/jbc.M115.671172<\/p>\n","source_link_url":"http:\/\/doi.org\/bbvp"}],"vf_locked":false,"featured":false,"color":"#007B53"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>One gene, two proteins, one complex | EMBL<\/title>\n<meta name=\"description\" content=\"Further insights into how viral enzymes degrade the cell walls of Clostridia bacteria.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"One gene, two proteins, one complex | EMBL\" \/>\n<meta property=\"og:description\" content=\"Further insights into how viral enzymes degrade the cell walls of Clostridia bacteria.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2016-01-15T14:19:15+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-25T09:34:13+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/01\/1601-endolysin-ib2.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Rosemary Wilson\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@rawilson80\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Rosemary Wilson\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\"},\"author\":{\"name\":\"Rosemary Wilson\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/bb5e57a6c6c5c3b33a6a40b2d4c96e40\"},\"headline\":\"One gene, two proteins, one complex\",\"datePublished\":\"2016-01-15T14:19:15+00:00\",\"dateModified\":\"2024-03-25T09:34:13+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\"},\"wordCount\":743,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/01\/1601-endolysin-ib2.jpg\",\"keywords\":[\"crystallography\",\"hamburg\",\"health\",\"meijers\",\"structural biology\"],\"articleSection\":[\"Science\",\"Science &amp; Technology\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\",\"url\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\",\"name\":\"One gene, two proteins, one complex | EMBL\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/01\/1601-endolysin-ib2.jpg\",\"datePublished\":\"2016-01-15T14:19:15+00:00\",\"dateModified\":\"2024-03-25T09:34:13+00:00\",\"description\":\"Further insights into how viral enzymes degrade the cell walls of Clostridia bacteria.\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1601-endolysin\/#primaryimage\",\"url\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/01\/1601-endolysin-ib2.jpg\",\"contentUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/01\/1601-endolysin-ib2.jpg\",\"width\":620,\"height\":425,\"caption\":\"Full length CTP1L protein (green) in complex with truncated C-terminal domain (violet). 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