PDB-101: Molecule of the Month: ATM and ATR Kinases

<!DOCTYPE html> <html> <head> <script src="https://www.googletagmanager.com/gtag/js?id=G-EPQ9202NVY" async></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); //- gtag('config', 'UA-71059016-1'); gtag('config', 'G-EPQ9202NVY'); </script> <title>PDB-101: Molecule of the Month: ATM and ATR Kinases</title> <meta charset="utf-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta property="og:title" content="PDB101: Molecule of the Month: ATM and ATR Kinases"> <meta property="og:description" content="Dividing cells use ATM and ATR kinases to respond to DNA damage."> <meta property="og:image" content="https://cdn.rcsb.org/pdb101/motm/284/ATM_ATR.jpg"> <meta property="og:url" content="http://pdb101.rcsb.org/motm/284"> <meta property="og:site_name" content="RCSB: PDB-101"> <meta name="twitter:card" content="summary"> <meta name="twitter:title" content="PDB101: Molecule of the Month: ATM and ATR Kinases"> <meta name="twitter:description" content="Dividing cells use ATM and ATR kinases to respond to DNA damage."> <meta name="twitter:image" content="https://cdn.rcsb.org/pdb101/motm/284/ATM_ATR.jpg"> <meta name="description" content="Dividing cells use ATM and ATR kinases to respond to DNA damage."> <meta name="keywords" content="DNA damage and repair,DNA,cell cycle,kinase,ATM,ATR,replication protein A,RPA,cancer 5np0,7ni5,5yz0,5dny,5gox,4gnx">  <meta name="google-site-verification" content="A8M31jAX8SUgQYzbnF5r-wgykna2i5Hp4J9fziVD9Sg"> <link href="https://cdn.rcsb.org/pdb101/common/jquery-ui-1.11.4/jquery-ui.min.css" rel="stylesheet"> <link href="https://cdn.rcsb.org/javascript/bootstrap/latest/css/bootstrap.min.css" rel="stylesheet"> <link href="/ekko-lightbox/ekko-lightbox.css" rel="stylesheet"> <link href="https://cdn.rcsb.org/javascript/fontawesome/latest/css/font-awesome.min.css" rel="stylesheet"> <link href="https://cdn.rcsb.org/javascript/timeline3/css/timeline.css" rel="stylesheet"> <link href="/css/style.css?v=20171201" rel="stylesheet"> <link href="https://cdn.rcsb.org/jira-feedback/css/jira-fdbck.css" rel="stylesheet"> <script src="https://cdn.rcsb.org/javascript/jquery/jquery-2.2.4.min.js"></script> <script src="https://cdn.rcsb.org/pdb101/common/jquery-ui-1.11.4/jquery-ui.min.js"></script> <script src="https://cdn.rcsb.org/javascript/bootstrap/latest/js/bootstrap.min.js"></script> <script src="/ekko-lightbox/ekko-lightbox.min.js"></script> <script src="/js/common.js"></script> <script src="https://cdn.rcsb.org/jira-feedback/js/jira-fdbck.min.js"></script> </head> <body> <div data-elastic-exclude> <nav class="navbar navbar-inverse navbar-fixed-top hidden-print"> <div class="container"> <div class="navbar-header"> <button type="button" data-toggle="collapse" data-target="#navbar" aria-expanded="false" aria-controls="navbar" class="navbar-toggle collapsed"><span class="sr-only">Toggle navigation</span><span class="icon-bar"></span><span class="icon-bar"></span><span class="icon-bar"></span></button><a href="/" class="navbar-brand">PDB-101</a> </div> <div id="navbar" class="collapse navbar-collapse"> <ul class="nav navbar-nav"> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle"><span class="hidden-sm hidden-xs">Molecule of the Month</span><span class="hidden-lg hidden-md">MotM</span><b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/motm">Current Feature</a></li> <li><a href="/motm/motm-by-category">By Category</a></li> <li><a href="/motm/motm-by-date">By Date</a></li> <li><a href="/motm/motm-by-title">By Title</a></li> <li><a href="/motm/motm-about">About Molecule of the Month</a></li> <li><a href="/motm/motm-image-download">Image Download</a></li> <li><a href="https://my.forms.app/rcsb-pdb/motm-newsletter" target="_blank">Newsletter Subscription</a></li> </ul> </li> <li><a href="/browse">Browse</a></li> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle">Learn<b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/learn/paper-models">Paper Models</a></li> <li><a href="/learn/flyers-posters-and-calendars">Flyers, Posters, & Calendars</a></li> <li><a href="/learn/videos">Videos</a></li> <li><a href="/learn/interactive-animations">Interactive Animations</a></li> <li><a href="/learn/coloring-books">Coloring Books</a></li> <li><a href="/learn/structural-biology-highlights">Structural Biology Highlights</a></li> <li><a href="/learn/3d-printing">3D Printing</a></li> <li><a href="/learn/exploring-the-structural-biology-of-cancer">Exploring the Structural Biology of Cancer</a></li> <li><a href="/learn/exploring-the-structural-biology-of-bioenergy">Exploring the Structural Biology of Bioenergy</a></li> <li><a href="/learn/exploring-the-structural-biology-of-viruses">Exploring the Structural Biology of Viruses</a></li> <li><a href="/learn/exploring-the-structural-biology-of-health-and-nutrition">Exploring the Structural Biology of Health and Nutrition</a></li> <li><a href="/learn/exploring-the-structural-biology-of-evolution">Exploring the Structural Biology of Evolution</a></li> <li><a href="/learn/exploring-structural-biology-with-computed-structure-models-csms">Exploring Structural Biology with Computed Structure Models (CSMs)</a></li> <li><a href="/learn/resources-to-fight-the-covid-19-pandemic">COVID-19 Pandemic Resources</a></li> <li><a href="/learn/other-resources">Other Resources</a></li> </ul> </li> <li class="dropdown"> <a href="#" data-toggle="dropdown" class="dropdown-toggle">Train <b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/train/guide-to-understanding-pdb-data/introduction">Guide to Understanding PDB Data</a></li> <li><a href="/train/training-events">Training Courses</a></li> <li><a href="/train/education-corner">Education Corner</a></li> <li><a href="/train/pdb-and-data-archiving-curriculum/about">PDB and Data Archiving Curriculum</a></li> </ul> </li> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle">Teach<b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/teach/overview">Overview of Curriculum Modules</a></li> <li role="separator" class="divider"></li>  <li><a href="/teach/biomolecular-structures-and-models" style="text-indent: 20px;">Biomolecular Structures and Models</a></li> <li><a href="/teach/covid-19/topics/getting-started-hand-washing" style="text-indent: 20px;">COVID-19 in Molecular Detail</a></li> <li><a href="/teach/diabetes-at-a-molecular-level" style="text-indent: 20px;">Diabetes at a Molecular Level</a></li> <li><a href="/teach/molecular-immunology" style="text-indent: 20px;">Molecular Immunology</a></li> <li><a href="/teach/molecular-view-of-hiv-aids" style="text-indent: 20px;">Molecular View of HIV/AIDS</a></li> <li><a href="/teach/box-of-lessons/topics/biological-macromolecules" style="text-indent: 20px;">Box of Lessons</a></li> </ul> </li> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle"><span class="hidden-sm hidden-xs">Global Health</span><span class="hidden-lg hidden-md">Health</span><b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/global-health/diabetes-mellitus/about/what-is-diabetes">Diabetes Mellitus</a></li> <li><a href="/global-health/cancer/about/what-is-cancer">Cancer </a></li> </ul> </li> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle">SciArt<b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/sci-art/geis-archive/about">Irving Geis</a></li> <li><a href="/sci-art/goodsell-gallery">David Goodsell</a></li> <li><a href="/sci-art/bezsonova-gallery">Irina Bezsonova</a></li> </ul> </li> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle">Events<b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/events/art-of-science">Art of Science</a></li> <li><a href="http://www.rcsb.org/pages/awards/poster_prize" target="_blank">Poster Prize </a></li> <p style="font-size: 90%; margin: 8px 15px 0 20px; font-weight: bold; margin-bottom: 0; border-top: 1px solid #ddd; padding-top: 5px">Past events</p> <li><a href="https://www.rcsb.org/pages/pdb50" target="_blank"> PDB50</a></li> <li><a href="/events/science-olympiad">Science Olympiad</a></li> <li><a href="/events/video-challenge/the-challenge">Video Challenge</a></li> </ul> </li> <li class="dropdown"><a href="#" data-toggle="dropdown" class="dropdown-toggle">About<b class="caret"></b></a> <ul class="dropdown-menu"> <li><a href="/more/about-pdb-101">About PDB-101</a></li> <li><a href="/more/contact-us">Contact us</a></li> <li><a href="/more/how-to-cite">How to Cite</a></li> <li><a href="https://www.rcsb.org/pages/about-us/pdb-user-community">User Community</a></li> <li><a href="https://www.rcsb.org/pages/about-us/deia">Diversity, Equity, Inclusion, and Access</a></li> </ul> </li> </ul> </div> </div> </nav> <style> /* search section */ #search-button { padding: 8px 15px; border-top-left-radius: 0; border-bottom-left-radius: 0; } #query-input { width: 100%; border: 1px solid #ccc; padding: 8px; } #query-input:focus { outline: none; } #query-table { width: 100%; } #query-table td:first-child { width: 100%; } #autosuggest { position: relative; width: 100%; text-align: left; } #autosuggest-items { position: absolute; border: 1px solid #eee; border-bottom: none; border-top: none; z-index: 99; top: 100%; left: 0; right: 0; } #autosuggest-items div { padding: 10px; cursor: pointer; background-color: #fff; border-bottom: 1px solid #d4d4d4; } #autosuggest-items div:hover { background-color: #e9e9e9; } .autosuggest-active { background-color: DodgerBlue !important; color: #fff; } </style> <div id="print-header" class="row"> <div class="col-xs-6"> <div id="pdb101-logo"><a href="/"><img src="https://cdn.rcsb.org/pdb101/common/images/logo-pdb101.png" alt="RCSB PDB"></a></div> </div> <div id="rcsb-logo" class="col-xs-6 text-right">Training and outreach portal of <a href='http://www.rcsb.org' target='_blank'><img src='https://cdn.rcsb.org/pdb101/common/images/logo-rcsb.png' height='57'></a></div> </div> <div id="header" class="hidden-print"> <div class="container"> <div style="margin-top:10px;" class="row"> <div id="logo_container" class="col-sm-12 col-md-6 hidden-xs"> <div id="pdb101-logo"><a href="/"><img src="https://cdn.rcsb.org/pdb101/common/images/logo-pdb101.png" alt="RCSB PDB"></a></div> <p style="margin-top: 7px;"><em>Molecular explorations<br />through biology and medicine</em></p> </div> <div style="margin-bottom:10px;" class="col-sm-12 col-md-6 text-right"> <form id="searchForm" action="/search" method="post" onsubmit="return validateQueryInput();" autocomplete="off"> <input type="hidden" name="querySource" value="user"> <table id="query-table"> <tr> <td> <div id="autosuggest"> <input id="query-input" type="text" name="query" value="" placeholder="Search Molecule of the Month articles and more"> <div id="autosuggest-items"></div> </div> </td> <td><span id="search-button" onclick="doSearch();" class="btn btn-primary">Go</span></td> </tr> </table> </form> </div> </div>   <div class="row"> <div style="margin:5px 0px;" class="col-xs-6 col-sm-6 col-md-6"> <table> <tr> <td>Training and outreach portal of&nbsp</td> <td rowspan="2"><a href='http://www.rcsb.org' target='_blank'><img src='https://cdn.rcsb.org/pdb101/common/images/logo-rcsb.png' width='75'></a></td> </tr> </table> </div> <div class="hidden-xs col-sm-6 col-md-6 col-lg-6 col-xl-6 text-right">       <div class="social-media"><a target="_blank" href="/motm/rss.xml" data-original-title="Molecule of the Month RSS Feed" data-toggle="tooltip"><i class="fa fa-rss-square fa-lg"></i></a><a target="_blank" href="https://www.facebook.com/RCSBPDB" data-original-title="Facebook" data-toggle="tooltip"><i class="fa fa-facebook-square fa-lg"></i></a><a target="_blank" href="https://twitter.com/buildmodels" data-original-title="Twitter" data-toggle="tooltip"><i class="fa fa-twitter fa-lg"></i></a><a target="_blank" href="https://www.youtube.com/user/RCSBProteinDataBank" data-original-title="YouTube" data-toggle="tooltip"><i class="fa fa-youtube-play fa-lg"></i></a><a target="_blank" href="https://github.com/rcsb" data-original-title="Github" data-toggle="tooltip"><i class="fa fa-github fa-lg"></i></a><a target="_blank" href="https://www.linkedin.com/company/rcsb-protein-data-bank/" data-original-title="LinkedIn" data-toggle="tooltip"><i class="fa fa-linkedin fa-lg"></i></a></div> </div> <div id="socialMedaiMobile" class="col-xs-6 hidden-sm hidden-md hidden-lg hidden-xl text-right"> <div class="social-media"><a target="_blank" href="/motm/rss.xml" data-original-title="Molecule of the Month RSS Feed" data-toggle="tooltip"><i class="fa fa-rss-square fa-lg"></i></a><a target="_blank" href="https://www.facebook.com/RCSBPDB" data-original-title="Facebook" data-toggle="tooltip"><i class="fa fa-facebook-square fa-lg"></i></a><a target="_blank" href="https://twitter.com/buildmodels" data-original-title="Twitter" data-toggle="tooltip"><i class="fa fa-twitter fa-lg"></i></a><a target="_blank" href="https://www.youtube.com/user/RCSBProteinDataBank" data-original-title="YouTube" data-toggle="tooltip"><i class="fa fa-youtube-play fa-lg"></i></a><a target="_blank" href="https://www.linkedin.com/company/rcsb-protein-data-bank/" data-original-title="LinkedIn" data-toggle="tooltip"><i class="fa fa-linkedin fa-lg"></i></a></div> </div> </div> </div> </div> <div id="main_content" class="container"> <style> #jmolTabs { margin: 20px 0; } .motm-hr { color: #ccc; background-color: #ccc; height: 1px; border: none; } .jmolText { font-family: 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; } /* over-write bootstrap values */ .nav-tabs { background: linear-gradient(to bottom, #fff, #ddd); } .tab-content { border-left: 1px solid #ddd; border-right: 1px solid #ddd; border-bottom: 1px solid #ddd; border-bottom-right-radius: 4px; border-bottom-left-radius: 4px; padding: 15px; } .nav-tabs > li.active > a, .nav-tabs > li.active > a:hover, .nav-tabs > li.active > a:focus { background-color: #fff; color: #333; } .tab-pane { padding-bottom: 10px; } #tabs-1 img { cursor: pointer; } .fa-cloud-download { margin-left:10px; } /* customize div.img-with-caption in style.css */ div.img-with-caption { max-width: 50%; margin-top: 10px; } div.float-right { float: right; margin-left: 20px; } div.float-left { float: left; margin-right: 20px; } .link-motm { background-color: #d9ebd294; padding: 10px; border-radius: 4px; border: 1px solid #bcedbd; overflow-wrap: break-word; } div.jmol-image { margin-bottom: 5px; } </style> <script> // jmol script var jmolLoaded = false function loadIframe() { if (jmolLoaded == false) { var src = '/motm/jmol/?id=' + 284 console.log('src=' + src) $("#iframe").attr('src', src) jmolLoaded = true } } function clickJmolTab() { $('#jmol-tab').trigger('click') } // jmol script for legacy motms with multiple jmols var jmols = []; function loadIframeById(jmolId) { var jmol = jmols[jmolId - 1] if (jmol.loaded == false) { var src = '/motm/jmol/?id=' + 284 + '&jmolId=' + jmolId $("#iframe_" + jmolId).attr('src', src) jmol.loaded = true } } function clickJmolTab(i) { var j = i + 1 $('#jmol-tab-' + j).trigger('click') } </script> <div id="sub-navbar"> <div class="row hidden-print"> <div class="col-xs-12 col-sm-6 sub-navbar"> <h4>Molecule of the Month</h4> </div> <div class="col-xs-12 col-sm-6 text-right sub-navbar"> <table> <tr> <td onclick="location.href="/motm/motm-by-category"">By Category</td> <td onclick="location.href="/motm/motm-by-date"">By Date</td> <td onclick="location.href="/motm/motm-by-title"">By Title</td> </tr> </table> </div> </div> </div> <div data-elastic-include> <h1>Molecule of the Month: ATM and ATR Kinases</h1> <p><i>Dividing cells use ATM and ATR kinases to respond to DNA damage.</i></p> <div> <div><i>This article was written and illustrated by Kamiel Beckley, Sarah McGuinness, Asya Polat and Kayla Puebla as part of a <a href="https://iqb.rutgers.edu/node/263">week-long boot camp</a> for undergraduate and graduate students hosted by the Rutgers Institute for Quantitative Biomedicine. The article is presented as part of the 2023-2024 PDB-101 health focus on “Cancer Biology and Therapeutics.”</i><br><br></div> <div class="img-with-caption float-right"> <div class="img-with-caption-table"><img src="https://cdn.rcsb.org/pdb101/motm/284/ATM_ATR.jpg" alt="ATM and ATR, with kinase domains in magenta, other domains in shades of purple, and ATR-interacting protein (ATRIP) in blue." class="img-responsive"> <div class="img-caption"> <div style="margin-bottom:10px;"><i>ATM and ATR, with kinase domains in magenta, other domains in shades of purple, and ATR-interacting protein (ATRIP) in blue.</i></div><a href="https://cdn.rcsb.org/pdb101/motm/284/ATM_ATR.tif"><small>Download high quality TIFF image<span class="fa fa-cloud-download"></span></small></a> </div> </div> </div> <div>As cells divide, they must ensure that their DNA is completely and accurately copied. Environmental dangers like UV radiation and toxic chemicals can damage DNA, and even normal cellular processes like DNA replication can have problems that lead to damage. Altogether, each cell has tens of thousands of sites of DNA damage every day. Failure to find and fix this DNA damage often leads to cancer. Our cells have checkpoints for recognizing broken DNA and pausing cell division until it is repaired. The protein kinases ATM (Ataxia-telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3-related protein) are crucial regulators of these DNA repair checkpoints. These proteins were identified while studying Ataxia telangiectasia, a complex neurodegenerative disease with immune system dysfunction, increased sensitivity to radiations, and predisposition to cancer. When DNA damage is identified, ATM and ATR work together to temporarily arrest the cell cycle and recruit proteins to repair it.</div> <h4>Signaling for Help</h4> <div>ATM and ATR notify the cell about different common types of DNA damage. While ATM focuses on double-strand breaks, which pose grave dangers to cells, ATR identifies single-stranded DNA, where a single unrepaired break may be enough to kill a cell. Single-stranded regions are normally formed during DNA replication, but if DNA polymerase stalls, helicases can continue unwinding the double helix, forming dangerously long single-stranded segments. Single-stranded DNA is also created at the ends of broken DNA during the process of repair, as the ends are trimmed before they are reconnected. When ATM and ATR find DNA damage, they phosphorylate and activate hundreds of proteins involved in management of the cell cycle and DNA repair. These include proteins such as <a href='/motm/31'>p53 tumor suppressor</a> and proteins such as <a href='/motm/172'>RAD51</a> of the homologous recombination pathway, a high-fidelity DNA repair process that uses an intact copy of the chromosome to repair and restore the damaged chromosome.</div> <h4>Called to Action</h4> <div>The basis of ATM and ATR signaling is now being revealed by cryoelectron microscopy. The 3D structure of human ATM is seen in PDB ID <a href='https://www.rcsb.org/structure/5np0' target='_blank'>5np0</a> and that of ATR is seen in PDB ID <a href='https://www.rcsb.org/structure/5yz0' target='_blank'>5yz0</a>, bound to ATRIP, a protein that helps mediate the interaction of ATR with proteins that bind to single-stranded DNA. ATM and ATR are members of the same protein family and both form huge butterfly-shaped complexes with several functional parts. The kinase domains (shown here in magenta) perform the phosphorylation reaction. The rest of the protein has several domains that are thought to mediate interactions with both specific sensors of damaged DNA and with the diverse proteins that are activated by phosphorylation.</div> </div> <div class="clearfix"></div> <hr class="motm-hr"> <div> <div class="img-with-caption float-left"> <div class="img-with-caption-table"><img src="https://cdn.rcsb.org/pdb101/motm/284/DNADamageSensors.jpg" alt="Proteins that sense damaged DNA. Rad50 and Mre11 are bound to a broken double-stranded DNA and replication protein A (RPA) is bound to single-stranded DNA. DNA is shown in yellow." class="img-responsive"> <div class="img-caption"> <div style="margin-bottom:10px;"><i>Proteins that sense damaged DNA. Rad50 and Mre11 are bound to a broken double-stranded DNA and replication protein A (RPA) is bound to single-stranded DNA. DNA is shown in yellow.</i></div><a href="https://cdn.rcsb.org/pdb101/motm/284/DNADamageSensors.tif"><small>Download high quality TIFF image<span class="fa fa-cloud-download"></span></small></a> </div> </div> </div> <h4>Heroes of the DNA Damage Response</h4> <div>ATM and ATR are key messengers in the DNA damage response. They rely on other proteins to find and recognize damaged DNA. Two examples are included here: a complex of Mre11 and Rad50 (PDB ID <a href='https://www.rcsb.org/structure/5dny' target='_blank'>5dny</a> and <a href='https://www.rcsb.org/structure/5gox' target='_blank'>5gox</a>) binds to double-strand breaks, and replication protein A (RPA, PDB ID <a href='https://www.rcsb.org/structure/4gnx' target='_blank'>4gnx</a>) binds to single-stranded DNA. These proteins then interact with ATM and ATR respectively, activating their kinase domains and allowing them to activate, in turn, the many proteins downstream in the cell cycle and repair pathways.</div> </div> <div class="clearfix"></div> <hr class="motm-hr"> <h4>Exploring the Structure</h4> <div id="jmolTabs" class="jmolText"> <ul class="nav nav-tabs"> <li class="active"><a data-toggle="tab" href="#tabs-1">Image</a></li> <li><a id="jmol-tab" data-toggle="tab" href="#tabs-2" onclick="loadIframe();">JSmol</a></li> </ul> <div class="tab-content"> <div id="tabs-1" class="tab-pane active"> <h5>ATM Complexes</h5> <div style="margin-top:0;" class="img-with-caption float-left"><img src="https://cdn.rcsb.org/pdb101/motm/284/Jmol-jmol.jpg" onclick="clickJmolTab();" class="img-responsive"></div> <p>Given their central roles in DNA repair, it is not surprising that ATM and ATR are intimately involved in development of cancer. Cancer cells often have mutated ATM and ATR that fail to stop cell division in cells with damaged genomes. Researchers are taking advantage of this last symptom to design drugs to block ATM. They are now looking for inhibitors to block ATM for use in cancer therapy. Although this may sound paradoxical, these drugs may be injected into tumors to make them more susceptible to radiation therapies. PDB ID <a href='https://www.rcsb.org/structure/7ni5' target='_blank'>7ni5</a> includes one of these experimental drugs bound to the kinase domain of ATM. The drug (green) binds in the same place as ATP (yellow, from PDB ID <a href='https://www.rcsb.org/structure/7ni6' target='_blank'>7ni6</a>) would bind, near three amino acids that catalyze the phosphorylation reaction (white). In the presence of the inhibitor, the enzyme does not bind ATP and cannot perform its kinase activity. <br> To explore these structures in more detail, click on the image for an interactive JSmol view.</p> <div class="clearfix"></div> </div> <div id="tabs-2" class="tab-pane"> <iframe id="iframe" marginheight="0" marginwidth="0" scrolling="yes" frameborder="0" width="100%"></iframe> </div> </div> </div> <div class="row"> <div class="col-xs-12 col-sm-12 col-md-6"> <h4>Topics for Further Discussion</h4> <ol> <li>ATM and ATR have been given different names in different organisms. For example, take a look at the yeast protein Tel1 (PDB ID <a href='https://www.rcsb.org/structure/6s8f' target='_blank'>6s8f</a>) and Mec1-Ddc2 (PDB ID <a href='https://www.rcsb.org/structure/6z3a' target='_blank'>6z3a</a>).</li> <li>You can use the sequence browser to explore the domain structure of these large proteins, which is available in a tab at the top of each Structure Summary Page. For example, <a href="https://www.rcsb.org/sequence/5NP0"> here’s the page for ATM.</a></li> </ol> <div data-elastic-exclude> <div class="col-xs-12 link-motm"> <h4>Related PDB-101 Resources</h4> <ul> <li>Browse <a href="/browse/cancer">Cancer</a></li> <li>Browse <a href="/browse/nucleic-acids">Nucleic Acids</a></li> <li>Browse <a href="/browse/cellular-signaling">Cellular Signaling</a></li> </ul> </div> </div> </div> <div style="border-left:1px dashed #ddd;" class="col-xs-12 col-sm-12 col-md-6"> <h4>References</h4> <ol> <li>Phan, L. M., Rezaeian, A. H. (2021) ATM: Main features, signaling pathways, and its diverse toles in DNA damage response, tumor suppression, and cancer development. Genes 12, 845. </li> <li>7ni5, 7ni6: Stakyte, K., Rotheneder, M., Lammens, K., Bartho, J. D., Gradler, U., Fuchs, T., Pehl, U., Alt, A., van de Logt, E., Hopfner, K. P. (2021) Molecular basis of human ATM kinase inhibition. Nat Struct Mol Biol 28, 789–798.</li> <li>6z3a: Tannous, E.A., Yates, L.A., Zhang, X., Burgers, P. M. (2021) Mechanism of auto-inhibition and activation of Mec1ATR checkpoint kinase. Nat Struct Mol Biol 28, 50–61.</li> <li>Williams, R. M., Yates, L. A., Zhang, X. (2020) Structures and regulations of ATM and ATR, master kinases in genome integrity. Curr Opin Struct Bio 61, 98–105.</li> <li>Sun, Y., McCorvie, T. J., Yates, L. A., Zhang, X. (2019) Structural basis of homologous recombination. Cell Molec Life Sci 77, 3–18.</li> <li>5np0: Baretic, D., Pollard, H.K., Fisher, D.I., Johnson, C.M., Santhanam, B., Truman, C.M., Kouba, T., Fersht, A.R., Phillips, C., Williams, R.L. (2017) Structures of closed and open conformations of dimeric human ATM. Sci Adv 3: e1700933-e1700933.</li> <li>5gox: Park, Y.B., Hohl, M., Padjasek, M., Jeong, E., Jin, K.S., Krezel, A., Petrini, J.H.J., Cho, Y. (2017) Eukaryotic Rad50 functions as a rod-shaped dimer. Nat Struct Mol Biol 24: 248-257.</li> <li>Rao, Q., Liu, M., Tian, Y., Wu, Z., Hao, Y., Song, L., Qin, Z., Ding, C., Wang, H.-W., Wang, J., Xu, Y. (2017) Cryo-EM structure of human ATR-ATRIP complex. Cell Research 28, 143–156.</li> <li>5dny: Liu, Y., Sung, S., Kim, Y., Li, F., Gwon, G., Jo, A., Kim, A.K., Kim, T., Song, O.K., Lee, S.E., Cho, Y. (2016) ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex. EMBO J 35: 743-758.</li> <li>Weber, A. M., Ryan, A. J. (2015) ATM and ATR as therapeutic targets in cancer. Pharmacology & therapeutics, 149, 124–138.</li> <li>Maréchal, A., Zou, L. (2013) DNA damage sensing by the ATM and ATR kinases. Cold Spring Harbor Persp Biol 5, a012716. </li> </ol> </div> </div> <hr class="motm-hr"> <p>August 2023, Kamiel Beckley, Sarah McGuinness, Asya Polat, Kayla Puebla, David S. Goodsell, Shuchismita Dutta</p> <a href="http://doi.org/10.2210/rcsb_pdb/mom_2023_8">http://doi.org/10.2210/rcsb_pdb/mom_2023_8</a> </div> <div style="margin-top:20px;" class="row hidden-print"> <div class="col-xs-12"> <div class="panel panel-info"> <div class="panel-heading">About Molecule of the Month</div> <div class="panel-body"><small> The RCSB PDB Molecule of the Month by David S. Goodsell (The Scripps Research Institute and the RCSB PDB) presents short accounts on selected molecules from the Protein Data Bank. Each installment includes an introduction to the structure and function of the molecule, a discussion of the relevance of the molecule to human health and welfare, and suggestions for how visitors might view these structures and access further details.<a href="/motm/motm-about">More</a></small> </div> </div> </div> </div> <script> $('#iframe').load(function () { $(this).height($(this).contents().find('body').height() + 30); }); </script> </div> <div id="footer_main" class="hidden-print"> <div class="container"> <div class="row"> <div class="col-sm-12 col-md-7"> <p><strong>About PDB-101</strong></p> <p>Researchers around the globe make 3D structures freely available from the Protein Data Bank (PDB) archive. PDB-101 training materials help graduate students, postdoctoral scholars, and researchers use PDB data and RCSB PDB tools. Outreach content demonstrate how PDB data impact fundamental biology, biomedicine, bioengineering/biotechnology, and energy sciences in 3D for a diverse and multidisciplinary user community. Education Materials provide lessons and activities for teaching and learning.</p> <p>PDB-101 is developed by the <a href="https://rcsb.org" target="_blank">RCSB PDB</a>.</p> </div> <div class="col-sm-12 col-md-5 text-center"> <p>RCSB PDB (<a href="http://nar.oxfordjournals.org/content/28/1/235.abstract" target="blank">citation</a>) is hosted by</p><img src="//cdn.rcsb.org/pdb101/common/images/Logo_Rutgers-2024.png" alt="Rutgers University logo" usemap="#rutgers-map" height="32" style="padding:0px 10px; border-right: 1px solid #000000;"><img src="//cdn.rcsb.org/pdb101/common/images/Logo_UCSD-SDSC.png" alt="University of California San Diego/San Diego Supercomputer Center logos" usemap="#UCSD-SDSC-map" height="26" style="padding: 0px 10px; border-right: 1px solid #000000;"><img src="//cdn.rcsb.org/pdb101/common/images/Logo_UCSF.png" alt="Univesity of California San Franciscologo" usemap="#UCSF-map" height="26" style="padding-left: 10px;"><map name="rutgers-map"> <area shape="rect" coords="0,0,115,26" href="http://www.rutgers.edu/" alt="Rutgers" target="_blank"></map><map name="UCSD-SDSC-map"> <area shape="rect" coords="0,0,150,26" href="http://ucsd.edu/" alt="UCSD" target="_blank"> <area shape="rect" coords="151,0,255,26" href="http://www.sdsc.edu/" alt="SDSC" target="_blank"></map><map name="UCSF-map"> <area shape="rect" coords="0,0,64,26" href="http://www.ucsf.edu/" alt="UCSF" target="_blank"></map><br><br> <p>RCSB PDB is a member of <span id='pdbmembers_footer'><a href='http://www.wwpdb.org/' target='_blank'><img src='//cdn.rcsb.org/pdb101/common/images/Logo_wwpdb.png' width='70'></a><span class='pipe'></span><a href='http://www.emdatabank.org/' target='_blank'><img src='https://cdn.rcsb.org/pdb101/common/images/EMDataResourcelogo.png' width='100'></a></p> </div> </div> </div> </div> <div id="footer_grant" class="hidden-print"> <div class="container"> <div class="row"> <p>RCSB PDB Core Operations are funded by the <a href="http://www.nsf.gov/" target="_blank">U.S. National Science Foundation</a> (DBI-2321666), the <a href="http://science.energy.gov/" target="_blank">US Department of Energy</a> (DE-SC0019749), and the <a href="http://www.cancer.gov/" target="_blank">National Cancer Institute</a>, <a href="http://www.niaid.nih.gov/" target="_blank">National Institute of Allergy and Infectious Diseases</a>, and <a href="http://www.nigms.nih.gov/" target="_blank">National Institute of General Medical Sciences</a> of the <a href="http://www.nih.gov/" target="_blank">National Institutes of Health</a> under grant R01GM157729.</p> </div> </div> </div> <div id="jira-fdbck"></div><script> //Google Analytics tracking code {/* (function(i,s,o,g,r,a,m){i['GoogleAnalyticsObject']=r;i[r]=i[r]||function(){ (i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o), m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m) })(window,document,'script','//www.google-analytics.com/analytics.js','ga'); ga('create', 'UA-71059016-1', 'auto'); ga('send', 'pageview'); */} </script> </div> </body> </html>

CINXE.COM

PDB-101: Molecule of the Month: ATM and ATR Kinases