{"id":25750,"date":"2011-10-13T18:00:00","date_gmt":"2011-10-13T16:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=25750"},"modified":"2024-11-14T16:29:36","modified_gmt":"2024-11-14T15:29:36","slug":"intruder-detected-raise-the-alarm","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/intruder-detected-raise-the-alarm\/","title":{"rendered":"Intruder detected: raise the alarm!"},"content":{"rendered":"\n<div class=\"wp-block-image\"><figure class=\"vf-figure  | vf-figure--align vf-figure--align-inline-start   size-medium is-resized\"><a href=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/rig-i.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/rig-i-214x300.jpg\" alt=\"In the absence of viral RNA (top), the part of RIG-I that senses viral RNA is exposed (orange), whilst the domains responsible for signalling (blue and pink) are out of reach of the signalling machinery. When RIG-I detects viral RNA, it changes shape (bottom), and the signalling domains become accessible to sound the alarm.\" class=\"wp-image-25760\" width=\"214\" height=\"300\" srcset=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/rig-i-214x300.jpg 214w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/rig-i.jpg 600w\" sizes=\"auto, (max-width: 214px) 100vw, 214px\" \/><\/a><figcaption class=\"vf-figure__caption\">In the absence of viral RNA (top), the part of RIG-I that senses viral RNA is exposed (orange), whilst the domains responsible for signalling (blue and pink) are out of reach of the signalling machinery. When RIG-I detects viral RNA, it changes shape (bottom), and the signalling domains become accessible to sound the alarm.\n\nClick on image to enlarge.\n\nCredit: EMBL\/Cusack.<\/figcaption><\/figure><\/div>\n\n\n\n<p>When a thief breaks into a bank vault, sensors are activated and the alarm is raised. Cells have their own early-warning system for intruders, and scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered how a particular protein sounds that alarm when it detects invading viruses. The study, published today in <em>Cell<\/em>, is a key development in our understanding of the innate immune response, shedding light on how cells rapidly respond to a wide range of viruses including influenza, rabies and hepatitis.<\/p>\n\n\n\n<p>To sense invading agents, cells use proteins called pattern recognition receptors, which recognise and bind to molecular signatures carried only by the intruder. This binding causes the receptors to change shape, starting a chain-reaction that ultimately alerts the surrounding cells to the invasion. How these two processes \u00ad\u2013 sensing and signalling \u2013 are connected, has until now remained unclear. The EMBL scientists have now discovered the precise structural mechanism by which one of these receptors, RIG-I, converts a change of shape into a signal.<\/p>\n\n\n\n<p>\u201cFor a structural biologist this is a classic question: how does ligand binding to a receptor induce signalling?\u201d says <a href=\"https:\/\/www.embl.org\/groups\/cusack\/\">Stephen Cusack<\/a>, who led the work. \u201cWe were particularly interested in answering it for RIG-I, as it targets practically all RNA viruses, including influenza, measles and hepatitis C.\u201d<\/p>\n\n\n\n<p>In response to a viral infection, RIG-I recognises viral genetic material \u2013 specifically, viral RNA \u2013 and primes the cell to produce the key anti-viral molecule, interferon. Interferon is secreted and picked up by surrounding cells, causing them to turn on hundreds of genes that act to combat the infection. To understand how RIG-I senses only viral RNA, and not the cell\u2019s own RNA, and sounds the alarm, the scientists used intense X-ray beams generated at the <a href=\"https:\/\/www.esrf.eu\/\" target=\"_blank\" rel=\"noreferrer noopener\">European Synchrotron Radiation Facility (ESRF)<\/a> to determine the three-dimensional atomic structure of RIG-I in the presence and absence of viral RNA, in a technique called X-ray crystallography. They found that in the absence of a viral infection, the receptor is \u2018sleeping with one eye open\u2019: the part of RIG-I that senses viral RNA is exposed, whilst the domains responsible for signalling are hidden, out of reach of the signalling machinery. When RIG-I detects viral RNA, it changes shape, \u2018waking up\u2019 the signalling domains, which become accessible to trigger interferon production. Although the EMBL scientists used RIG-I from the mallard duck, this receptor\u2019s behaviour is identical to that of its human counterpart.<\/p>\n\n\n\n<p>\u201cRIG-I is activated in response to viral RNA, but a similar mechanism is likely to be used by a number of other immune receptors, whether they are specific to viruses or bacteria,\u201d says PhD student Eva Kowalinski, who carried out most of the work.&nbsp;<\/p>\n\n\n\n<p>Thus, these findings contribute to a broader understanding of the workings of the innate immune system \u2013 our first line of defence against intruders, and the subject of this year\u2019s Nobel Prize in Physiology or Medicine.&nbsp;The work was carried out within the framework of the International Unit of Virus Host-Cell Interactions, a collaboration between EMBL, the University Joseph Fourier (UJF), in Grenoble, and the French Centre National de la Recherche Scientifique (CNRS) and also involved contributions from the laboratory of Denis Gerlier at the Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), in Lyon, France.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>When a thief breaks into a bank vault, sensors are activated and the alarm is raised. Cells have their own early-warning system for intruders, and scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered how a particular protein sounds that alarm when it&hellip;<\/p>\n","protected":false},"author":16,"featured_media":25760,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[335,37,1748],"embl_taxonomy":[],"class_list":["post-25750","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-cusack","tag-grenoble","tag-press-release"],"acf":{"show_featured_image":true,"vf_locked":false,"featured":false,"article_intro":"<p>How a molecular switch activates the anti-viral innate immune response<\/p>\n","article_sources":[{"source_description":"<p>Kowalinski, E., Lunardi, T., McCarthy, A.A., Louber, J., Brunel, J., Grigorov, B., Gerlier, D. &amp; Cusack, S. Structural basis for the activation of innate immune pattern recognition receptor RIG-I by viral RNA. <em>Cell<\/em>, 14 October 2011. DOI:10.1016\/j.cell.2011.09.039<\/p>\n","source_link_url":"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867411011500?via%3Dihub"}],"related_links":false,"in_this_article":false,"color":"#007B53","link_color":"#fff","youtube_url":"","mp4_url":"","video_caption":"","press_contact":"EMBL Generic","field_target_display":"embl","source_article":false},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Intruder detected: raise the alarm! | EMBL<\/title>\n<meta name=\"description\" content=\"Scientists at EMBL have discovered how a particular protein sounds that alarm when it detects invading viruses.\" \/>\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\/intruder-detected-raise-the-alarm\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Intruder detected: raise the alarm! 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