{"id":5080,"date":"2019-09-29T17:25:04","date_gmt":"2019-09-29T16:25:04","guid":{"rendered":"https:\/\/www.blopig.com\/blog\/?p=5080"},"modified":"2019-10-01T16:11:34","modified_gmt":"2019-10-01T15:11:34","slug":"a-collection-of-prion-factoids","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2019\/09\/a-collection-of-prion-factoids\/","title":{"rendered":"A collection of prion factoids"},"content":{"rendered":"\n<p>It&#8217;s been several years since I last presented a talk on prions to OPIG, so I thought a neat way of getting up to date would be to read &#8220;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30646817\/\">The prion 2018 round tables<\/a>&#8220;.  What&#8217;s the current understanding and are we any closer to determining a structure of PrP<sup>Sc<\/sup>?<\/p>\n\n\n\n<!--more-->\n\n\n\n<p>In short, we now know a lot more than we used to.  However this is one of those problems where the more you know, the harder the problem becomes.<\/p>\n\n\n\n<p>There are currently two proposed structures for PrP<sup>Sc<\/sup>  :  <\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>PIRBS &#8211; Parallel In-Register Beta Sheets<\/li><li>\u03b2-solenoids <\/li><\/ul>\n\n\n\n<p>Experiments published in peer-reviewed journals in <a href=\"https:\/\/www.pnas.org\/content\/104\/48\/18946\">2007<\/a>, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3025268\/\">2010 <\/a>and <a href=\"http:\/\/www.jbc.org\/content\/289\/35\/24129.abstract\">2014<\/a>, performed in different labs and using techniques including site-specific spin labeling as well as solid-state NMR have shown that PIRBS is a likely structure.  <\/p>\n\n\n\n<p>Whilst it is enormously difficult to determine the structure of brain-derived PrP<sup>Sc<\/sup>, subsections of it can be expressed which can be more readily defined.   In position 145, a tyrosine to stop codon mutation can be used to provide a truncated PIRBS-shaped PrP <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28963458?dopt=Abstract\">fragment<\/a>.  In fact, even this remarkably small fragment (PrP23-144) has been shown to be <a href=\"https:\/\/www.pnas.org\/content\/113\/48\/13851\">infectious<\/a>.<\/p>\n\n\n\n<p>On the other hand, there is strong evidence that PrP<sup>Sc<\/sup> has a \u03b2-solenoid structure.  This has been determined by both Cryo-EM and by Solid-State NMR by at least two <a href=\"https:\/\/journals.plos.org\/plospathogens\/article?id=10.1371\/journal.ppat.1005835\">different<\/a> research <a href=\"https:\/\/science.sciencemag.org\/content\/319\/5869\/1523\">groups<\/a>.   As mentioned in the paper &#8220;The 4-rung \u03b2-solenoid model agrees with experimental constraints of brain derived PrP<sup>Sc<\/sup>&#8221;  <\/p>\n\n\n\n<p>Not being an experimentalist, I&#8217;ve got no right or reason to wade in on which structure is more likely.  This leaves the question, is what was once a difficult problem now compounded by there being two different strains of  PrP<sup>Sc<\/sup>?  Possibly.  Our unknown structure(s) of PrP<sup>Sc<\/sup> form through an unknown post-translational mechanism.  But to make a difficult job harder, the paper concludes: &#8220;PIRIBS structures might be able to template 4-rung \u03b2-solenoids and 4-rung \u03b2-solenoids might template PIRIBS amyloids, as was seen in <a href=\"https:\/\/www.pnas.org\/content\/104\/52\/20914\">the amyloid seeding assay<\/a>&#8220;. <\/p>\n\n\n\n<p>That&#8217;s right, our unknown \u03b2-solenoid, may through an unknown mechanism, template an unknown PIRBS structure&nbsp;and via another unknown mechanism, vice versa.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>It&#8217;s been several years since I last presented a talk on prions to OPIG, so I thought a neat way of getting up to date would be to read &#8220;The prion 2018 round tables&#8220;. What&#8217;s the current understanding and are we any closer to determining a structure of PrPSc?<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","wikipediapreview_detectlinks":true,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"ngg_post_thumbnail":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[123,10,228,202,9],"tags":[],"ppma_author":[507],"class_list":["post-5080","post","type-post","status-publish","format-standard","hentry","category-commentary","category-groupmeetings","category-protein-structure","category-proteins","category-talks"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"authors":[{"term_id":507,"user_id":15,"is_guest":0,"slug":"eoin","display_name":"Eoin Malins","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/e91a9cf8b77625a1bc34e56f5dc36439a1f61476804b087e5b47554425879210?s=96&d=mm&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/5080","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/comments?post=5080"}],"version-history":[{"count":5,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/5080\/revisions"}],"predecessor-version":[{"id":5097,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/5080\/revisions\/5097"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=5080"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=5080"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=5080"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=5080"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}