{"id":3135,"date":"2025-02-05T20:45:32","date_gmt":"2025-02-06T01:45:32","guid":{"rendered":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/?p=3135"},"modified":"2025-02-05T20:45:32","modified_gmt":"2025-02-06T01:45:32","slug":"new-paper-on-intermediate-gpcr-g-protein-complex","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/2025\/02\/new-paper-on-intermediate-gpcr-g-protein-complex\/","title":{"rendered":"New paper on Intermediate GPCR-G protein complex!"},"content":{"rendered":"<p>Congratulations to Jinan and Victor in our lab for a collaborative paper published in Nature Communications on Jan 28, 2025 (Chinese New Year day!): &#8220;<a href=\"https:\/\/www.nature.com\/articles\/s41467-025-56434-4\"><strong>Structure and function of a near fully-activated intermediate GPCR-G\u03b1\u03b2\u03b3 complex<\/strong><\/a>&#8220;. Thanks to Prof. Libin Ye&#8217;s lab at University of South Florida and Prof. Yifan Cheng&#8217;s lab at University of California San Francisco for the great collaboration!<\/p>\n<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Abstract<\/h2>\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<p>Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-G\u03b1\u03b2\u03b3 structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive. Guided by a conformational landscape visualized via\u00a0<sup>19<\/sup>F quantitative NMR and molecular dynamics (MD) simulations, we determined the structure of an intermediate GPCR-mini-G\u03b1<sub>s<\/sub>\u03b2\u03b3 complex at 2.6\u2009\u00c5 using cryo-EM, by blocking its transition to the fully activated complex. Furthermore, we present direct evidence that the complex at this intermediate state initiates a rate-limited nucleotide exchange before transitioning to the fully activated complex. In this state, BODIPY-GDP\/GTP based nucleotide exchange assays further indicated the \u03b1-helical domain of the G\u03b1 is partially open, allowing it to grasp a nucleotide at a non-canonical binding site, distinct from the canonical nucleotide-binding site. These advances bridge a significant gap in our understanding of the complexity of GPCR signaling.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Congratulations to Jinan and Victor in our lab for a collaborative paper published in Nature Communications on Jan 28, 2025 (Chinese New Year day!): &#8220;Structure and function of a near fully-activated intermediate GPCR-G\u03b1\u03b2\u03b3 complex&#8220;. Thanks to Prof. Libin Ye&#8217;s lab at University of South Florida and Prof. Yifan Cheng&#8217;s lab at University of California San &hellip; <a href=\"https:\/\/www.med.unc.edu\/pharm\/miaolab\/2025\/02\/new-paper-on-intermediate-gpcr-g-protein-complex\/\" aria-label=\"Read more about New paper on Intermediate GPCR-G protein complex!\">Read more<\/a><\/p>\n","protected":false},"author":115433,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[1],"tags":[],"class_list":["post-3135","post","type-post","status-publish","format-standard","hentry","category-news","odd"],"acf":[],"featured_image":false,"featured_image_medium":false,"featured_image_medium_large":false,"featured_image_large":false,"featured_image_thumbnail":false,"featured_image_alt":false,"category_details":[{"name":"News","link":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/category\/news\/"}],"tag_details":[],"_links_to":[],"_links_to_target":[],"_links":{"self":[{"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/posts\/3135","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/users\/115433"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/comments?post=3135"}],"version-history":[{"count":0,"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/posts\/3135\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/media?parent=3135"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/categories?post=3135"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.med.unc.edu\/pharm\/miaolab\/wp-json\/wp\/v2\/tags?post=3135"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}