{"id":2710,"date":"2021-03-27T13:41:59","date_gmt":"2021-03-27T20:41:59","guid":{"rendered":"http:\/\/blogs.oregonstate.edu\/psquared\/?page_id=2710"},"modified":"2023-05-17T13:51:19","modified_gmt":"2023-05-17T20:51:19","slug":"getting-comfortable-with-protein-domains","status":"publish","type":"page","link":"https:\/\/blogs.oregonstate.edu\/psquared\/getting-comfortable-with-protein-domains\/","title":{"rendered":"Getting comfortable with protein domains"},"content":{"rendered":"<h2>Protein domains<\/h2>\n<p>Domains are compact arrangements of folded chains. \u00a0From a purely artistic perspective, you can think of a\u00a0domain as a\u00a0major substructure (a chunk)\u00a0of the overall protein. \u00a0A domain stands apart from the rest of the structure. If a protein were a human body, the head would be one of its domains, the trunk another, the left arm another, etc. \u00a0Some proteins have a single domain, others have\u00a0many. \u00a0A chain sometimes folds into a single domain , sometimes into multiple domains. \u00a0For example, an <a href=\"https:\/\/pdb101.rcsb.org\/motm\/21\">IgG molecule<\/a> (the main type of antibody molecule in the blood) includes four chains folded into six domains.<\/p>\n<div style=\"width: 207px\" class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/cdn.rcsb.org\/pdb101\/geis\/images\/1000w\/geis-0437-immunoglobulin-g.png\" alt=\"Antibody structure by Geis\" width=\"197\" height=\"245\" \/><p class=\"wp-caption-text\">Antibody structure, by Geis<\/p><\/div>\n<p>One of the great discoveries of the past decade is the conservation of domains across all of biology. \u00a0The biological world includes a few hundred domains as the canonical elements that account for the structures and functions of\u00a0essentially all of the many thousands of existing\u00a0proteins. \u00a0Long ago\u00a0nature evidently discovered a set of compact machines (domains) and has used them creatively in assorted mix-and-match combinations. \u00a0This is amazing: \u00a0The many thousands of known protein structures (they all can be looked up in the PDB!) fold into just a few hundred generic protein domains.<\/p>\n<ul>\n<li>For the artist, one very helpful exercise is to make\u00a02-D sketches\u00a0of 3-D proteins. \u00a0A 2-D &#8220;topological diagram&#8221; can serve as\u00a0a quick and easy surrogate for\u00a0a rotatable 3D computer model when\u00a0you are trying to make sense of how a chain travels through a molecule. \u00a0Below are examples from\u00a0<a href=\"http:\/\/kinemage.biochem.duke.edu\/teaching\/anatax\/index.html\">Jane Richardson<\/a>. \u00a0She is deservedly credited as the inventor of 2-D topological sketches of proteins. Note how her topo diagrams readily highlight the differences between superficially \u00a0similar alpha-beta class proteins:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-2828\" src=\"https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2023\/05\/Jane_Richardson_topo_photo-300x127.png\" alt=\"\" width=\"496\" height=\"210\" srcset=\"https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2023\/05\/Jane_Richardson_topo_photo-300x127.png 300w, https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2023\/05\/Jane_Richardson_topo_photo-1024x432.png 1024w, https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2023\/05\/Jane_Richardson_topo_photo-768x324.png 768w, https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2023\/05\/Jane_Richardson_topo_photo.png 1356w\" sizes=\"auto, (max-width: 496px) 100vw, 496px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li>An artist can take advantage of 2-D topologies while attempting to depict\u00a0the complicated multi-domain and \u00a0oligomeric-structure of big protein molecules. \u00a0No matter which depiction the artist has in mind, it is useful to make some 2D top0 sketches: \u00a0Will you depict a small protein by showing its details, or will you smudge out the detail and portray a big protein? \u00a0The sketch book is your friend!<\/li>\n<\/ul>\n<h2>Examples of protein domains<\/h2>\n<p>Proteins adopt shapes that are related to each other in discernible ways that beg for classification schemes that help us to make sense out of complexity in sort of the same way that the Linnaean classification scheme allows us to compare zebras and horses and sharks and then proclaim that two of those three are more closely related.<\/p>\n<p>Below is a sampling of some of the thousands of ways that protein chains fold into <em>domains<\/em>. A domain is simply a discernible shape, often repeated in related proteins, often explanatory of the function of the protein. \u00a0A protein may consist of a single domain, and more complicated proteins are assemblages of numerous domains. \u00a0If the human body were a single protein molecule, one might claim that it includes a single head domain but also several other domains that might be lumped together as appendage domains or more narrowly defined as hand domains and feet domains, for example.<\/p>\n<p><a href=\"http:\/\/blogs.oregonstate.edu\/psquared\/files\/2012\/04\/gkn877f1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-1278 size-full\" src=\"https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2012\/04\/gkn877f1.jpg\" alt=\"\" width=\"478\" height=\"398\" srcset=\"https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2012\/04\/gkn877f1.jpg 478w, https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2012\/04\/gkn877f1-300x249.jpg 300w, https:\/\/osu-wams-blogs-uploads.s3.amazonaws.com\/blogs.dir\/150\/files\/2012\/04\/gkn877f1-400x333.jpg 400w\" sizes=\"auto, (max-width: 478px) 100vw, 478px\" \/><\/a><\/p>\n<h2>How to classify domains?<\/h2>\n<p>The people who study protein domains scientifically are often artists at heart. \u00a0This is also a great field for those interested in classification and bioinformatics. \u00a0Some very large and interesting databases have been created to help keep track of the families of proteins as arranged according to domain structure. \u00a0One of the well-known databases is called CATH. \u00a0Another is SCOP. \u00a0The following quotation (which announced CATH to the world) gives you an idea of how such classifications are organized.<\/p>\n<p style=\"padding-left: 40px\">&#8220;<strong>CATH<\/strong> (class, architecture, topology, homology) is a hierarchical protein domain classification (1) where domains are classified manually by curators, guided by prediction algorithms (such as structure comparison). Each protein structure is decomposed into one or more chains which in turn are split into one or more domains before being classified into homologous superfamilies according to both structure and function. At the <strong>Class<\/strong>, or C-level, the domains are classified simply on the basis of their secondary structure content [whether they are mostly \u03b1-helical (Class 1) or \u03b2-sheet (Class 2), contain a significant percentage of both secondary structure elements (Class 3) or contain very little secondary structure (Class 4)]. The domains within each class are then sorted according to their <strong>architecture<\/strong>\u2014that is similarities in the arrangements of secondary structures in 3D space. Each architecture (A-level) is further broken down into one or more <strong>topology<\/strong>, or fold, groups (T-level), where the connectivity between these secondary structures are taken into account. The domains are then classified into their respective <strong>homologous superfamilies<\/strong> (H-level) according to similarities in sequence, structure and\/or function. Clustering performed at the H-level (&gt;35% sequence identity and above) then produces one or more sequence families for each of the homologous superfamilies (S-level).&#8221;<\/p>\n<p style=\"padding-left: 40px\">&#8211;From:\u00a0<span style=\"text-decoration: underline\">Nucleic Acids Res<\/span>. 2009 January; 37 (Database issue): D310\u2013D314.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Protein domains Domains are compact arrangements of folded chains. \u00a0From a purely artistic perspective, you can think of a\u00a0domain as a\u00a0major substructure (a chunk)\u00a0of the overall protein. \u00a0A domain stands apart from the rest of the structure. If a protein &hellip; <a href=\"https:\/\/blogs.oregonstate.edu\/psquared\/getting-comfortable-with-protein-domains\/\">Continue reading <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":196,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-2710","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/pages\/2710","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/users\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/comments?post=2710"}],"version-history":[{"count":9,"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/pages\/2710\/revisions"}],"predecessor-version":[{"id":2744,"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/pages\/2710\/revisions\/2744"}],"wp:attachment":[{"href":"https:\/\/blogs.oregonstate.edu\/psquared\/wp-json\/wp\/v2\/media?parent=2710"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}