{"id":31148,"date":"2020-08-18T16:00:00","date_gmt":"2020-08-18T14:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=31148"},"modified":"2024-03-22T11:01:14","modified_gmt":"2024-03-22T10:01:14","slug":"flexible-corona","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/flexible-corona\/","title":{"rendered":"Flexible and protected \u2013 new findings on SARS-CoV-2 protein shed light on virus\u2019s ability to infect cells"},"content":{"rendered":"\n<p>At the start of a COVID-19 infection, the coronavirus SARS-CoV-2 docks onto human cells using the spike-like proteins on its surface. The spike protein is at the centre of vaccine development because it triggers an immune response in humans. A group of German scientists, including members of EMBL in Heidelberg, the <a href=\"https:\/\/www.biophys.mpg.de\/en\">Max Planck Institute of Biophysics<\/a>, the <a href=\"https:\/\/www.pei.de\">Paul-Ehrlich-Institut<\/a>, and <a href=\"https:\/\/www.goethe-university-frankfurt.de\">Goethe University Frankfurt<\/a> have focused on the surface structure of the virus to gain insights they can use for the development of vaccines and of effective therapeutics to treat infected patients.<\/p>\n\n\n\n<p>The team combined cryo-electron tomography, subtomogram averaging, and molecular dynamics simulations to analyse the molecular structure of the spike protein in its natural environment, on intact virions, and with near-atomic resolution. Using EMBL\u2019s state-of-the-art <a href=\"https:\/\/www.embl.de\/services\/cryo-em-platform\/\">cryo-electron microscopy imaging facility<\/a>, 266 cryotomograms of about 1000 different viruses were generated, each carrying an average of 40 spikes on its surface. Subtomogram averaging and image processing, combined with molecular dynamics simulations, finally provided the important and novel structural information on these spikes.<\/p>\n\n\n\n<p>The results were surprising: the data showed that the globular portion of the spike protein, which contains the receptor-binding region and the machinery required for fusion with the target cell, is connected to a flexible stalk. \u201cThe upper spherical part of the spike has a structure that is well reproduced by recombinant proteins used for vaccine development,\u201d explains Martin Beck, EMBL group leader and a director of the Max Planck Institute (MPI) of Biophysics. \u201cHowever, our findings about the stalk, which fixes the globular part of the spike protein to the virus surface, were new.\u201d<\/p>\n\n\n\n<figure class=\"wp-block-embed-youtube wp-block-embed is-type-video is-provider-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<iframe loading=\"lazy\" title=\"EMBL\u2019s infrastructure and expertise sheds light on the ability of SARS-CoV-2 to infect cells\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/se692WfwQU0?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe>\n<\/div><figcaption>Gerhard Hummer, Jacomine Krijnse Locker and Martin Beck talk about their research and their cooperation with EMBL.<br \/>Credit: EMBL<\/figcaption><\/figure>\n\n\n\n<p>\u201cThe stalk was expected to be quite rigid,\u201d adds Gerhard Hummer, from the MPI of Biophysics and the Institute of Biophysics at Goethe University Frankfurt. \u201cBut in our computer models and in the actual images, we discovered that the stalks are extremely flexible.\u201d By combining molecular dynamics simulations and cryo-electron tomography, the team identified the three joints \u2013 hip, knee and ankle \u2013 that give the stalk its flexibility.<\/p>\n\n\n\n<p>\u201cLike a balloon on a string, the spikes appear to move on the surface of the virus and thus are able to search for the receptor for docking to the target cell,\u201d explains Jacomine Krijnse Locker, group leader at the Paul-Ehrlich-Institut. To prevent infection, these spikes are targeted by antibodies. However, the images and models also showed that the entire spike protein, including the stalk, is covered with chains of glycans \u2013 sugar-like molecules. These chains provide a kind of protective coat that hides the spikes from neutralising antibodies: another important finding on the way to effective vaccines and medicines.<\/p>\n\n\n\n<hr class=\"vf-divider\"\/>\n\n\n\n<h1 class=\"wp-block-heading\" id=\"german\">Flexibel und gesch\u00fctzt &#8211; Neue Erkenntnisse \u00fcber ein SARS-CoV-2-Protein geben Aufschluss \u00fcber die F\u00e4higkeit des Virus, Zellen zu infizieren<\/h1>\n\n\n\n<p class=\"vf-u-margin__bottom--md\"><\/p>\n\n\n<p class=\"vf-lede\">Im Kampf gegen das Coronavirus haben Forscher von SARS-CoV-2 aus mehreren Forschungseinrichtungen in Deutschland ihre Ressourcen geb\u00fcndelt, um das Spike-Protein auf der Oberfl\u00e4che des Virus zu untersuchen. Mit diesen Stacheln bindet sich das Virus an menschliche Zellen und infiziert sie. Die Studie ergab \u00fcberraschende Einblicke in das Spike-Protein, darunter eine unerwartete Bewegungsfreiheit und eine Schutzh\u00fclle, die es vor Antik\u00f6rpern versteckt. Die Ergebnisse wurden in <em>Science<\/em> ver\u00f6ffentlicht.<\/p>\n\n\n\n<p class=\"vf-u-margin__bottom--md\"><\/p>\n\n\n\n<div class=\"vf-embed vf-embed--16x9 | vf-u-margin__bottom--400\">\n<iframe src=\"https:\/\/www.youtube.com\/embed\/_mUg-XIU0nQ\" frameborder=\"0\" controls allowfullscreen><\/iframe><\/div>\n\n  \n<figcaption class=\"vf-figure__caption vf-u-margin__top--200\">Dies ist eine Simulation von vier Spike-Proteinen (rot, orange, blau und grau) des SARS-CoV-2-Virus. Die Proteine und Lipide sind in Oberfl\u00e4chendarstellung dargestellt. Die sch\u00fctzenden Glykanketten sind gr\u00fcn gef\u00e4rbt. Videonachweis: S\u00f6ren von B\u00fclow, Mateusz Sikora, Gerhard Hummer\/MPI of Biophysics<\/figcaption>\n\n\n\n\n\n<p>Zu Beginn einer COVID-19-Infektion dockt das Coronavirus SARS-CoV-2 mit Hilfe von Stachel-\u00e4hnlichen Proteinen an seiner Oberfl\u00e4che an menschliche Zellen an. Dieses Protein steht im Zentrum der Impfstoffentwicklung, weil es beim Menschen eine Immunantwort ausl\u00f6st. Eine Gruppe deutscher Wissenschaftler, darunter Mitglieder des EMBL in Heidelberg, des <a href=\"https:\/\/www.biophys.mpg.de\">Max-Planck-Instituts f\u00fcr Biophysik<\/a>, des <a href=\"https:\/\/www.pei.de\/\">Paul-Ehrlich-Instituts<\/a> und der <a href=\"https:\/\/www.goethe-university-frankfurt.de\/\">Goethe-Universit\u00e4t Frankfurt<\/a>, hat sich mit der Oberfl\u00e4chenstruktur des Virus befasst, um Erkenntnisse zu gewinnen, die f\u00fcr die Entwicklung von Impfstoffen und wirksamen Therapeutika zur Behandlung infizierter Patienten benutzt werden k\u00f6nnen.<\/p>\n\n\n\n<p>Das Team kombinierte Kryo-Elektronentomographie, Subtomogramm-Mittelung und Molekulardynamik-Simulationen, um die molekulare Struktur des Spike-Proteins in seiner nat\u00fcrlichen Umgebung, an intakten Viren und mit nahezu atomarer Aufl\u00f6sung zu analysieren. Mit Hilfe der hochmoderne<a href=\"https:\/\/www.embl.de\/services\/cryo-em-platform\/\">n Kryo-Elektronenmikroskopie-Bildgebungsanlage des EMBL<\/a> wurden 266 Kryotomogramme von etwa 1000 verschiedenen Viren erzeugt, von denen jedes durchschnittlich 40 Spike-Proteine auf seiner Oberfl\u00e4che tr\u00e4gt. Subtomogramm-Mittelung und Bildverarbeitung, kombiniert mit Molekulardynamik-Simulationen, lieferten schlie\u00dflich die wichtigen und neuartigen strukturellen Informationen zu diesen Stacheln.<\/p>\n\n\n\n<p>Die Ergebnisse waren \u00fcberraschend: Die Daten zeigten, dass der kugelf\u00f6rmige Teil des Spike-Proteins, der die rezeptorbindende Region und die f\u00fcr die Fusion mit der Zielzelle erforderliche Maschinerie enth\u00e4lt, mit einem flexiblen Stiel verbunden ist. \u201eDer obere kugelf\u00f6rmige Teil des Spike-Proteins hat eine Struktur, die von rekombinanten Proteinen, die f\u00fcr die Impfstoffentwicklung verwendet werden, gut reproduziert wird,&#8221; erkl\u00e4rt Martin Beck, Gruppenleiter am EMBL und Direktor des Max-Planck-Instituts (MPI) f\u00fcr Biophysik. \u201eUnsere Erkenntnisse \u00fcber den Stiel, der den kugelf\u00f6rmigen Teil des Spike-Proteins an der Virusoberfl\u00e4che fixiert, waren jedoch neu.\u201c<\/p>\n\n\n\n<p>\u201eEs wurde erwartet, dass der Stiel ziemlich starr sein w\u00fcrde,&#8221; f\u00fcgt Gerhard Hummer vom MPI f\u00fcr Biophysik und dem Institut f\u00fcr Biophysik der Goethe-Universit\u00e4t Frankfurt hinzu. \u201eAber in unseren Computermodellen und in den tats\u00e4chlichen Bildern entdeckten wir, dass die St\u00e4ngel extrem flexibel sind. Durch die Kombination von Molekulardynamiksimulationen und Kryo-Elektronentomographie identifizierte das Team die drei Gelenke \u2013 H\u00fcfte, Knie und Kn\u00f6chel \u2013, die dem St\u00e4ngel seine Flexibilit\u00e4t verleihen. \u201eWie ein Ballon an einer Schnur scheinen sich die St\u00e4ngel auf der Oberfl\u00e4che des Virus zu bewegen und k\u00f6nnen so nach dem Rezeptor f\u00fcr das Andocken an die Zielzelle suchen,\u201c erkl\u00e4rt Jacomine Krijnse Locker, Gruppenleiterin am Paul-Ehrlich-Institut. Um eine Infektion zu verhindern, werden diese Stacheln von Antik\u00f6rpern angegriffen. Die Bilder und Modelle zeigten aber auch, dass das gesamte Spike-Protein, einschlie\u00dflich des Stiels, mit Ketten aus Glykanen \u2013 zucker\u00e4hnlichen Molek\u00fclen \u2013 bedeckt ist. Diese Ketten bilden eine Art Schutzmantel, der die Stacheln vor neutralisierenden Antik\u00f6rpern verbirgt: eine weitere wichtige Erkenntnis auf dem Weg zu wirksamen Impfstoffen und Medikamenten.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Researchers studied the spike protein on the surface of the SARS-CoV-2 virus. With its spikes, the virus binds to human cells and infects them. The study gave surprising insights into the spike protein, including an unexpected freedom of movement and a protective coat to hide it from antibodies.<\/p>\n","protected":false},"author":71,"featured_media":31162,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[1331,718,616,1329],"embl_taxonomy":[2278,1812],"class_list":["post-31148","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-covid-19","tag-cryo-em","tag-protein","tag-sars-cov-2","embl_taxonomy-covid-19","embl_taxonomy-microscopy"],"acf":{"featured":true,"show_featured_image":false,"color":"#007B53","link_color":"#fff","article_intro":"<p>In the fight against the coronavirus, SARS-CoV-2 researchers from multiple research institutions in Germany have combined their resources to study the spike protein on the surface of the virus. With its spikes, the virus binds to human cells and infects them. The study gave surprising insights into the spike protein, including an unexpected freedom of movement and a protective coat to hide it from antibodies. The results are published in <em>Science<\/em>.<\/p>\n","related_links":[{"link_description":"Paul-Ehrlich-Institut","link_url":"https:\/\/www.pei.de\/"},{"link_description":"Max Planck Institute of Biophysics","link_url":"https:\/\/www.biophys.mpg.de\/en"},{"link_description":"Goethe University Frankfurt","link_url":"https:\/\/www.goethe-university-frankfurt.de\/"}],"article_sources":[{"source_description":"<p>Beata Turo\u0148ov\u00e1, <em>et al<\/em>. <em>In situ<\/em> structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. <em>Science<\/em>, published online 18 August 2020,<br \/>\nDOI: 10.1126\/science.abd5223<\/p>\n","source_link_url":"https:\/\/science.sciencemag.org\/lookup\/doi\/10.1126\/science.abd5223"}],"in_this_article":false,"youtube_url":"https:\/\/www.youtube.com\/embed\/_mUg-XIU0nQ","mp4_url":"","video_caption":"This is a simulation of four spike proteins (red, orange, blue and grey) of the SARS-CoV-2 virus. The proteins and lipids are shown in surface representation. The protective glycan chains are shown in green. Credit: S\u00f6ren von B\u00fclow, Mateusz Sikora, Gerhard Hummer\/MPI of Biophysics","press_contact":"EMBL Generic","translations":[{"translation_language":"Catalan","translation_anchor":"#german"}],"vf_locked":false,"embl_taxonomy_term_who":false,"embl_taxonomy_term_what":false,"embl_taxonomy_term_where":false},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"a5d0c484-f12a-4a27-93cc-85e3a6d79c09\";i:2;s:36:\"5683518e-43cd-4740-8583-31a65ef324d3\";}","parents":[],"name":["COVID-19"],"slug":"covid-19","description":"What &gt; Topics &gt; COVID-19"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"ef0437fc-a5b7-4c73-bcfd-63bff16cb35e\";i:2;s:36:\"4821b240-af78-4dc6-89a8-1dc7c2436c57\";}","parents":[],"name":["Microscopy"],"slug":"microscopy","description":"What &gt; Services and facilities &gt; Microscopy"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Flexible and protected \u2013 new findings on SARS-CoV-2 protein shed light on virus\u2019s ability to infect cells | EMBL<\/title>\n<meta name=\"description\" content=\"A study on the SARS-CoV-2 spike protein gave new insights, including a protective coat to hide it from antibodies.\" \/>\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\/flexible-corona\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Flexible and protected \u2013 new findings on SARS-CoV-2 protein shed light on virus\u2019s ability to infect cells | EMBL\" \/>\n<meta property=\"og:description\" content=\"A study on the SARS-CoV-2 spike protein gave new insights, including a protective coat to hide it from antibodies.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/flexible-corona\/\" \/>\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=\"2020-08-18T14:00:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-22T10:01:14+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/08\/covid-spikes.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1000\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Mathias J\u00e4ger\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Mathias J\u00e4ger\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 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\/flexible-corona\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/flexible-corona\/\"},\"author\":{\"name\":\"Mathias J\u00e4ger\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/63a0ca26daa6707834de41dfddfc6a42\"},\"headline\":\"Flexible and protected \u2013 new findings on SARS-CoV-2 protein shed light on virus\u2019s ability to infect cells\",\"datePublished\":\"2020-08-18T14:00:00+00:00\",\"dateModified\":\"2024-03-22T10:01:14+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/flexible-corona\/\"},\"wordCount\":934,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/flexible-corona\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/08\/covid-spikes.jpg\",\"keywords\":[\"covid-19\",\"cryo-em\",\"protein\",\"sars-cov-2\"],\"articleSection\":[\"Science\",\"Science &amp; 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