Structural basis for motilin and erythromycin recognition by motilin receptor
Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macr...
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| Veröffentlicht in: | Science advances 2023-03, Vol.9 (11), p.eade9020-eade9020 |
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| creator | You, Chongzhao Zhang, Yumu Xu, Youwei Xu, Peiyu Li, Zhen Li, Huadong Huang, Sijie Chen, Zecai Li, Jingru Xu, H Eric Jiang, Yi |
| description | Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of G
-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders. |
| doi_str_mv | 10.1126/sciadv.ade9020 |
| format | Article |
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-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.ade9020</identifier><identifier>PMID: 36921049</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Biomedicine and Life Sciences ; Erythromycin - metabolism ; Erythromycin - pharmacology ; Humans ; Motilin - metabolism ; Receptors, Gastrointestinal Hormone - chemistry ; Receptors, Gastrointestinal Hormone - metabolism ; Receptors, Neuropeptide - metabolism ; SciAdv r-articles ; Signal Transduction ; Structural Biology</subject><ispartof>Science advances, 2023-03, Vol.9 (11), p.eade9020-eade9020</ispartof><rights>Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2023 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-b1fb625d3ba7a3a9524bc06975260ad7a949230882a9e51947e50caee6bf7a993</citedby><cites>FETCH-LOGICAL-c391t-b1fb625d3ba7a3a9524bc06975260ad7a949230882a9e51947e50caee6bf7a993</cites><orcidid>0000-0002-0723-1413 ; 0000-0001-8069-7511 ; 0000-0003-3590-4037 ; 0000-0002-6425-3387 ; 0000-0002-5204-473X ; 0000-0002-6829-8144</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017046/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017046/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36921049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>You, Chongzhao</creatorcontrib><creatorcontrib>Zhang, Yumu</creatorcontrib><creatorcontrib>Xu, Youwei</creatorcontrib><creatorcontrib>Xu, Peiyu</creatorcontrib><creatorcontrib>Li, Zhen</creatorcontrib><creatorcontrib>Li, Huadong</creatorcontrib><creatorcontrib>Huang, Sijie</creatorcontrib><creatorcontrib>Chen, Zecai</creatorcontrib><creatorcontrib>Li, Jingru</creatorcontrib><creatorcontrib>Xu, H Eric</creatorcontrib><creatorcontrib>Jiang, Yi</creatorcontrib><title>Structural basis for motilin and erythromycin recognition by motilin receptor</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of G
-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders.</description><subject>Biomedicine and Life Sciences</subject><subject>Erythromycin - metabolism</subject><subject>Erythromycin - pharmacology</subject><subject>Humans</subject><subject>Motilin - metabolism</subject><subject>Receptors, Gastrointestinal Hormone - chemistry</subject><subject>Receptors, Gastrointestinal Hormone - metabolism</subject><subject>Receptors, Neuropeptide - metabolism</subject><subject>SciAdv r-articles</subject><subject>Signal Transduction</subject><subject>Structural Biology</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctOwzAQtBCIVtArR5QjlxQ_Yjs-IVTxkoo4AGfLcZzWKImL7VTK32PUUpXTrnZmZx8DwBWCc4Qwuw3aqno7V7UREMMTMMWE0xzTojw9yidgFsIXhBAVjFEkzsGEMIERLMQUvL5HP-g4eNVmlQo2ZI3zWeeibW2fqb7OjB_j2rtu1KngjXar3kbr-qwaD7xUNpvo_CU4a1QbzGwfL8Dn48PH4jlfvj29LO6XuSYCxbxCTcUwrUmluCJKUFxUGjLBKWZQ1VyJQmACyxIrYdLGBTcUamUMq5oECnIB7na6m6HqTK1NH9MBcuNtp_wonbLyP9LbtVy5rUTpCxwWLCnc7BW8-x5MiLKzQZu2Vb1xQ5CYlyUXlJAyUec7qvYuBG-awxwE5a8PcueD3PuQGq6PtzvQ_75OfgBjJ4fP</recordid><startdate>20230317</startdate><enddate>20230317</enddate><creator>You, Chongzhao</creator><creator>Zhang, Yumu</creator><creator>Xu, Youwei</creator><creator>Xu, Peiyu</creator><creator>Li, Zhen</creator><creator>Li, Huadong</creator><creator>Huang, Sijie</creator><creator>Chen, Zecai</creator><creator>Li, Jingru</creator><creator>Xu, H Eric</creator><creator>Jiang, Yi</creator><general>American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0723-1413</orcidid><orcidid>https://orcid.org/0000-0001-8069-7511</orcidid><orcidid>https://orcid.org/0000-0003-3590-4037</orcidid><orcidid>https://orcid.org/0000-0002-6425-3387</orcidid><orcidid>https://orcid.org/0000-0002-5204-473X</orcidid><orcidid>https://orcid.org/0000-0002-6829-8144</orcidid></search><sort><creationdate>20230317</creationdate><title>Structural basis for motilin and erythromycin recognition by motilin receptor</title><author>You, Chongzhao ; 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It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of G
-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>36921049</pmid><doi>10.1126/sciadv.ade9020</doi><orcidid>https://orcid.org/0000-0002-0723-1413</orcidid><orcidid>https://orcid.org/0000-0001-8069-7511</orcidid><orcidid>https://orcid.org/0000-0003-3590-4037</orcidid><orcidid>https://orcid.org/0000-0002-6425-3387</orcidid><orcidid>https://orcid.org/0000-0002-5204-473X</orcidid><orcidid>https://orcid.org/0000-0002-6829-8144</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biomedicine and Life Sciences Erythromycin - metabolism Erythromycin - pharmacology Humans Motilin - metabolism Receptors, Gastrointestinal Hormone - chemistry Receptors, Gastrointestinal Hormone - metabolism Receptors, Neuropeptide - metabolism SciAdv r-articles Signal Transduction Structural Biology |
| title | Structural basis for motilin and erythromycin recognition by motilin receptor |
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