{"id":169,"date":"2013-02-11T01:03:14","date_gmt":"2013-02-11T01:03:14","guid":{"rendered":"http:\/\/blopig.com\/blog\/?p=169"},"modified":"2013-02-11T01:19:40","modified_gmt":"2013-02-11T01:19:40","slug":"conservation-of-kinks-in-membrane-proteins","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2013\/02\/conservation-of-kinks-in-membrane-proteins\/","title":{"rendered":"Conservation of kinks in membrane proteins"},"content":{"rendered":"<p>In my Part II project, I have been comparing pairs of homologous alpha-helical transmembrane proteins from the <a href=\"http:\/\/www.rcsb.org\/pdb\/home\/home.do\" target=\"_blank\">PDB<\/a>, looking specifically at how often kinks are conserved. Kinks are of particular interest in membrane protein structure as they can\u00a0<a title=\"Conformational dynamics of helix S6 from Shaker potassium channel: Simulation studies\" href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bip.10197\/full\" target=\"_blank\">introduce flexibility<\/a>\u00a0for movement between conformations and\u00a0are\u00a0therefore important for function.<\/p>\n<p><a href=\"https:\/\/i0.wp.com\/blopig.com\/blog\/wp-content\/uploads\/2013\/02\/helices.png\"><img data-recalc-dims=\"1\" decoding=\"async\" loading=\"lazy\" class=\"alignnone size-medium wp-image-170\" alt=\"helices\" src=\"https:\/\/i0.wp.com\/blopig.com\/blog\/wp-content\/uploads\/2013\/02\/helices-297x300.png?resize=297%2C300\" width=\"297\" height=\"300\" srcset=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2013\/02\/helices.png?resize=297%2C300&amp;ssl=1 297w, https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2013\/02\/helices.png?w=406&amp;ssl=1 406w\" sizes=\"auto, (max-width: 297px) 100vw, 297px\" \/><\/a><\/p>\n<p><span style=\"line-height: 1.714285714;font-size: 1rem\">Kinks typically involve some disruption of the usual pattern of hydrogen bonding in the helix, so proline is frequently found at the location of helix kinks due to its lack of an N-H group. However, there are many kinks where proline is not present, and <\/span><a style=\"line-height: 1.714285714;font-size: 1rem\" title=\"The evolution of transmembrane helix kinks and the structural diversity of G protein-coupled receptors\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC327124\/\" target=\"_blank\">mutation of a proline residue to alanine<\/a><span style=\"line-height: 1.714285714;font-size: 1rem\"> at the site of a kink does not necessarily lead to removal of the kink. This led to the suggestion that all kinks are originally caused by prolines, but consequent changes to the surrounding structure mean that the kink can be retained even when a mutation occurs at a later point. Therefore I have particularly been looking at the incidence of prolines around kinks in the pairs of homologous helices.<\/span><\/p>\n<p>In order to find kinks in helices I have been using two different programs: Kink Finder, written by <a title=\"Henry Wilman\" href=\"http:\/\/users.ox.ac.uk\/~hert2742\/\" target=\"_blank\">Henry<\/a>, another member of the group, and <a href=\"http:\/\/structbio.biochem.dal.ca\/jrainey\/MC-HELAN\/\" target=\"_blank\">MC-HELAN<\/a>. Kink Finder fits cylinders to a helix to measure angles at each residue, while MC-HELAN finds sections of ideal helix and labels any overlapping sections as kinks. These contrasting methods both\u00a0<span style=\"font-size: 1rem\">indicate the extent of the kink by\u00a0<\/span><span style=\"line-height: 1.714285714;font-size: 1rem\">giving an angle between the axes fitted to sections of helix on either side. <\/span><a style=\"line-height: 1.714285714;font-size: 1rem\" href=\"http:\/\/zhanglab.ccmb.med.umich.edu\/TM-align\/\" target=\"_blank\">TM-align<\/a><span style=\"line-height: 1.714285714;font-size: 1rem\"> and\u00a0<\/span><a style=\"line-height: 1.714285714;font-size: 1rem\" href=\"http:\/\/www.stats.ox.ac.uk\/research\/proteins\/resources\" target=\"_blank\">MP-T<\/a><span style=\"line-height: 1.714285714;font-size: 1rem\">\u00a0have both been used to align the pairs of proteins and find homologous helices, and I am also looking at the multiple sequence alignments provided by MP-T to question whether proline can always be found in a homolog at the position of the kink, even if it is not present in the protein itself.<\/span><\/p>\n<p>This work will hopefully give a better indication of when kinks should be predicted, particularly when using a program such as <a href=\"http:\/\/opig.stats.ox.ac.uk\/webapps\/medeller\/gui\/home.pl?app=medeller\" target=\"_blank\">MEDELLER<\/a> to predict membrane protein structure by homology modelling. If it were known in which circumstances a kink could be confidently predicted as conserved, the accuracy of the prediction of membrane regions could be further improved.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>In my Part II project, I have been comparing pairs of homologous alpha-helical transmembrane proteins from the PDB, looking specifically at how often kinks are conserved. Kinks are of particular interest in membrane protein structure as they can\u00a0introduce flexibility\u00a0for movement between conformations and\u00a0are\u00a0therefore important for function. Kinks typically involve some disruption of the usual pattern [&hellip;]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","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":[10],"tags":[],"ppma_author":[503],"class_list":["post-169","post","type-post","status-publish","format-standard","hentry","category-groupmeetings"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"authors":[{"term_id":503,"user_id":7,"is_guest":0,"slug":"eleanor","display_name":"Eleanor Law","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/55139eec0fe9cd58b650c1c3e8624dc0b15f54d9dabda63560ab5eb6b521d213?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\/169","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\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/comments?post=169"}],"version-history":[{"count":9,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/169\/revisions"}],"predecessor-version":[{"id":177,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/169\/revisions\/177"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=169"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=169"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=169"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=169"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}