{"id":1711,"date":"2023-07-07T07:07:24","date_gmt":"2023-07-07T14:07:24","guid":{"rendered":"https:\/\/sites.bioe.uw.edu\/daggett\/?page_id=1711"},"modified":"2023-07-07T07:38:19","modified_gmt":"2023-07-07T14:38:19","slug":"%ce%b1-sheet-in-amyloid-diseases","status":"publish","type":"page","link":"https:\/\/sites.bioe.uw.edu\/daggett\/research\/%ce%b1-sheet-in-amyloid-diseases\/","title":{"rendered":"\u03b1-sheet in Amyloid Diseases"},"content":{"rendered":"<div  class=\"grid row equal   \" >\n<div  class=\"col-sm\">\n<div class=\"info-box full-width\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-thumbnail wp-image-1715\" src=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/Amyloidogenic-Protein-Examples-1-150x150.png\" alt=\" Amyloidogenic Protein Examples\" width=\"150\" height=\"150\" \/><br \/>\n<em>Native crystal structures for four amyloidogenic proteins (top) and their conversion to \u03b1-sheet (red strands, lower structures) during MD simulations at low pH with all native disulfide bonds intact. <a href=\"http:\/\/dx.doi.org\/10.1021\/ar0500719\">(image source)<\/a><\/em><\/div>\n<\/div>\n<div  class=\"col-sm\">\n<div class=\"info-box full-width\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-thumbnail wp-image-1716\" src=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/TTR-150x150.png\" alt=\" The DAGH \u03b2-sheet from the transthyretin crystal structure and after MD at low pH. \" width=\"150\" height=\"150\" \/><br \/>\n<em>The DAGH \u03b2-sheet from the transthyretin crystal structure and after MD at low pH.\u00a0<a href=\"http:\/\/dx.doi.org\/10.1021\/ar0500719\">(image source)<\/a><\/em><\/div>\n<\/div>\n<div  class=\"col-sm\">\n<div class=\"info-box full-width\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-thumbnail wp-image-1717\" src=\"https:\/\/sites.bioe.uw.edu\/daggett\/wp-content\/uploads\/sites\/47\/2023\/07\/alpha_strand_and_sheet_in_lysozyme-150x150.png\" alt=\"alpha strand and sheet in lysozyme\" width=\"150\" height=\"150\" \/><br \/>\n<em>\u03b1-Strand and \u03b1-sheet structure in lysozyme:\u2009 (A) \u03b1-strand structure in hen egg white lysozyme crystal structure; (B) conversion to \u03b1-sheet in MD simulation of human variant at low pH and a model of an \u03b1-sheet aggregate. <a href=\"http:\/\/dx.doi.org\/10.1021\/ar0500719\">(image source)<\/a><\/em><\/div>\n<\/div>\n<\/div>\n<p>There are now over 50 known amyloid diseases that affect a variety of tissues throughout the body. Amyloid diseases are characterized by the aggregation of peptide\/protein monomers into toxic, soluble oligomers, and eventually mature, insoluble plaques that are relatively nontoxic. We have proposed that \u03b1-sheet plays a critical role in both the aggregation and toxicity of soluble oligomers.<\/p>\n<p>Our work with disease systems revolves around the design of templated \u03b1-sheet peptides that inhibit aggregation and mitigate toxicity of the amyloid species <em>in vitro<\/em> and <em>in vivo<\/em>. We use a variety of standard and novel techniques to help us define the role of \u03b1-sheet in amyloid diseases, including: spectroscopic characterizations; cell-based assays; testing in relevant animal disease models; and structure-based assays. We have found a strong correlation between \u03b1-sheet content and toxicity and are developing a plate-based Soluble Oligomer Binding Assay (SOBA) for detection of toxic species.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>There are now over 50 known amyloid diseases that affect a variety of tissues throughout the body. Amyloid diseases are characterized by the aggregation of peptide\/protein monomers into toxic, soluble oligomers, and eventually mature, insoluble plaques that are relatively nontoxic. We have proposed that \u03b1-sheet plays a critical role in both the aggregation and toxicity of soluble oligomers. Our work with disease systems revolves around the design of templated \u03b1-sheet peptides that inhibit aggregation and mitigate toxicity of the amyloid&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":197,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1711","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/1711","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=1711"}],"version-history":[{"count":8,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/1711\/revisions"}],"predecessor-version":[{"id":1723,"href":"https:\/\/sites.bioe.uw.edu\/daggett\/wp-json\/wp\/v2\/pages\/1711\/revisions\/1723"}],"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=1711"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}