{"id":2701,"date":"2023-02-02T10:54:14","date_gmt":"2023-02-02T01:54:14","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=2701"},"modified":"2023-02-02T15:28:29","modified_gmt":"2023-02-02T06:28:29","slug":"ligand-recognition-and-allosteric-modulation-of-the-human-mrgprx1-receptor","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=2701","title":{"rendered":"Ligand recognition and allosteric modulation of the human MRGPRX1 receptor"},"content":{"rendered":"\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Liu+Y&amp;cauthor_id=36302898\">Yongfeng Liu<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#equal-contrib-explanation\">#<\/a><\/sup><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-2\">2<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Cao+C&amp;cauthor_id=36302898\">Can Cao<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#equal-contrib-explanation\">#<\/a><\/sup><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Huang+XP&amp;cauthor_id=36302898\">Xi-Ping Huang<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-2\">2<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Gumpper+RH&amp;cauthor_id=36302898\">Ryan H Gumpper<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Rachman+MM&amp;cauthor_id=36302898\">Moira M Rachman<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-3\">3<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Shih+SL&amp;cauthor_id=36302898\">Sheng-Luen Shih<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-2\">2<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Krumm+BE&amp;cauthor_id=36302898\">Brian E Krumm<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zhang+S&amp;cauthor_id=36302898\">Shicheng Zhang<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-1\">1<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Shoichet+BK&amp;cauthor_id=36302898\">Brian K Shoichet<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-3\">3<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Fay+JF&amp;cauthor_id=36302898\">Jonathan F Fay<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-4\">4<\/a>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-5\">5<\/a><\/sup>,&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Roth+BL&amp;cauthor_id=36302898\">Bryan L Roth<\/a><sup>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-6\">6<\/a>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-7\">7<\/a>&nbsp;<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36302898\/?utm_source=FeedFetcher&amp;utm_medium=rss&amp;utm_campaign=None&amp;utm_content=161WTD0KV8_jVME-cADgRamkLSHyGP4XV5Tinopyy93kT3rIMS&amp;fc=None&amp;ff=20221028161447&amp;v=2.17.8#affiliation-8\">8<\/a><\/sup><\/p>\n\n\n\n<ul id=\"full-view-identifiers\"><li>PMID:&nbsp;<strong>36302898<\/strong><\/li><li>DOI:&nbsp;<a target=\"_blank\" rel=\"noreferrer noopener\" href=\"https:\/\/doi.org\/10.1038\/s41589-022-01173-6\">10.1038\/s41589-022-01173-6<\/a><\/li><\/ul>\n\n\n\n<h2>Abstract<\/h2>\n\n\n\n<p>The human MAS-related G protein-coupled receptor X1 (MRGPRX1) is preferentially expressed in the small-diameter primary sensory neurons and involved in the mediation of nociception and pruritus. Central activation of MRGPRX1 by the endogenous opioid peptide fragment BAM8-22 and its positive allosteric modulator ML382 has been shown to effectively inhibit persistent pain, making MRGPRX1 a promising target for non-opioid pain treatment. However, the activation mechanism of MRGPRX1 is still largely unknown. Here we report three high-resolution cryogenic electron microscopy structures of MRGPRX1-G\u03b1q in complex with BAM8-22 alone, with BAM8-22 and ML382 simultaneously as well as with a synthetic agonist compound-16. These structures reveal the agonist binding mode for MRGPRX1 and illuminate the structural requirements for positive allosteric modulation. Collectively, our findings provide a molecular understanding of the activation and allosteric modulation of the MRGPRX1 receptor, which could facilitate the structure-based design of non-opioid pain-relieving drugs.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<div class=\"wp-block-file\"><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2023\/02\/Ligand-recognition-and-allosteric-modulation-of-the-human-MRGPRX1-receptor.pdf\">Ligand recognition and allosteric modulation of the human MRGPRX1 receptor.<\/a><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2023\/02\/Ligand-recognition-and-allosteric-modulation-of-the-human-MRGPRX1-receptor.pdf\" class=\"wp-block-file__button\" download>Download<\/a><\/div>\n\n\n\n<div class=\"wp-block-file\"><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2023\/02\/Supplementary-Information.pdf\">Supplementary Information<\/a><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2023\/02\/Supplementary-Information.pdf\" class=\"wp-block-file__button\" download>Download<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Yongfeng Liu&nbsp;#&nbsp;1&nbsp;2,&nbsp;Can Cao&nbsp;#&nbsp;1,&nbsp;Xi-Ping Huang&nbsp;1&nbsp;2,&nbsp;Ryan H Gumpper&nbsp;1,&nbsp;Moira M Rachman&nbsp;3,&nbsp;Sheng-Luen Shih&nbsp;1&nbsp;2,&nbsp;Brian E Krumm&nbsp;1,&nbsp;Shicheng Zhang&nbsp;1,&nbsp;Brian K Shoichet&nbsp;3,&nbsp;Jonathan F Fay&nbsp;4&nbsp;5,&nbsp;Bryan L Roth&nbsp;6&nbsp;7&nbsp;8 PMID:&nbsp;36302898 DOI:&nbsp;10.1038\/s41589-022-01173-6 Abstract The human MAS-related G protein-coupled receptor X1 (MRGPRX1) is preferentially expressed in the small-diameter primary sensory neurons and involved in the mediation of nociception and pruritus. Central activation of MRGPRX1 by the endogenous opioid [&hellip;]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2701"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2701"}],"version-history":[{"count":3,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2701\/revisions"}],"predecessor-version":[{"id":2706,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2701\/revisions\/2706"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2701"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2701"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2701"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}