{"id":1737,"date":"2023-07-07T08:26:06","date_gmt":"2023-07-07T15:26:06","guid":{"rendered":"https:\/\/sites.bioe.uw.edu\/daggett\/?page_id=1737"},"modified":"2023-07-07T09:16:59","modified_gmt":"2023-07-07T16:16:59","slug":"characterizing-the-%ce%b1-sheet-structure","status":"publish","type":"page","link":"https:\/\/sites.bioe.uw.edu\/daggett\/research\/characterizing-the-%ce%b1-sheet-structure\/","title":{"rendered":"Characterizing the \u03b1-sheet Structure"},"content":{"rendered":"<div  class=\"grid row equal   \" >\n<div  class=\"col-9\">\n<figure id=\"attachment_1738\" aria-describedby=\"caption-attachment-1738\" style=\"width: 1024px\" class=\"figure figure-caption wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-1738 size-large\" src=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-1024x354.png\" alt=\"Beta to Alpha\" width=\"1024\" height=\"354\" srcset=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-1024x354.png 1024w, https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-300x104.png 300w, https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-768x265.png 768w, https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-1536x531.png 1536w, https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-375x130.png 375w, https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha-1200x415.png 1200w, https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/beta_to_alpha.png 1737w\" sizes=\"auto, 100vw\" \/><figcaption id=\"caption-attachment-1738\" class=\"wp-caption-text\"><em>Structural difference between \u03b1- and \u03b2-sheet. \u03b1-sheet is a protein secondary structure composed of residues in an alternating \u03b1R \u03b1L pattern.<\/em> <\/figcaption><\/figure>\n<\/div>\n<div  class=\"col-3\">\n<figure id=\"attachment_1759\" aria-describedby=\"caption-attachment-1759\" style=\"width: 205px\" class=\"figure figure-caption wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-1759\" src=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/molecular-simulation.gif\" alt=\"Molecular simulation depicting the formation of \u03b1-sheet.\" width=\"205\" height=\"200\" \/><figcaption id=\"caption-attachment-1759\" class=\"wp-caption-text\"><em>Molecular simulation depicting the formation of \u03b1-sheet.<\/em> <\/figcaption><\/figure>\n<\/div>\n<\/div>\n<figure id=\"attachment_1771\" aria-describedby=\"caption-attachment-1771\" style=\"width: 150px\" class=\"figure figure-caption wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"size-thumbnail wp-image-1771\" src=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/cd-150x150.jpg\" alt=\"Circular Dichroism (CD) spectrum depicting the differences between \u03b1-sheet, \u03b2-sheet, and random coils.\" width=\"150\" height=\"150\" \/><figcaption id=\"caption-attachment-1771\" class=\"wp-caption-text\"><em>Circular Dichroism (CD) spectrum depicting the differences between \u03b1-sheet, \u03b2-sheet, and random coils.<\/em> <\/figcaption><\/figure>\n<p>There are now over X human peptides and proteins associated with amyloid disease and the formation of insoluble, fibrillar deposits. Interestingly, these proteins share little in common \u2013 they have variable native topologies and secondary structure content (some are even natively disordered), amino acid composition, and native functions. Despite these differences, the resulting mature fibrils and intermediate species share many characteristics.<\/p>\n<p>Traditionally, the formulation of diagnostic and\/or therapeutic strategies requires structural insight into the target protein. However, the heterogeneous \u2013 and potentially disordered \u2013 ensemble of intermediate amyloid species largely preclude structural insight through traditional methods such as X-ray crystallography or NMR spectroscopy. To fill this gap, we perform atomistic simulations of amyloid proteins under amyloidogenic conditions to model the early conformational changes that occur during amyloidogenesis.<\/p>\n<p>In simulations of multiple proteins\u00a0\u2013 including transthyretin, superoxide dismutase, prion, and lysozyme \u2013 we have observed the formation of an unusual type of secondary structure that we have dubbed \u2018\u03b1-sheet\u2019. The unique properties of this secondary structure have guided our lab\u2019s central hypothesis regarding amyloidogenesis and led to the development of peptides capable of inhibiting amyloid formation in multiple systems.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>There are now over X human peptides and proteins associated with amyloid disease and the formation of insoluble, fibrillar deposits. Interestingly, these proteins share little in common \u2013 they have variable native topologies and secondary structure content (some are even natively disordered), amino acid composition, and native functions. Despite these differences, the resulting mature fibrils and intermediate species share many characteristics. Traditionally, the formulation of diagnostic and\/or therapeutic strategies requires structural insight into the target protein. However, the heterogeneous \u2013&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":197,"menu_order":4,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1737","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/1737","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/comments?post=1737"}],"version-history":[{"count":27,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/1737\/revisions"}],"predecessor-version":[{"id":1772,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/1737\/revisions\/1772"}],"up":[{"embeddable":true,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/197"}],"wp:attachment":[{"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/media?parent=1737"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}