{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:56:39Z","timestamp":1785426999101,"version":"3.56.0"},"reference-count":45,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Science and Technology Major Project"},{"name":"Lingang Laboratory grant","award":["LG202102-01-01"],"award-info":[{"award-number":["LG202102-01-01"]}]},{"name":"Lingang Laboratory grant","award":["LG-QS-202206-08"],"award-info":[{"award-number":["LG-QS-202206-08"]}]},{"name":"Fund of Youth Innovation Promotion Association","award":["2022077"],"award-info":[{"award-number":["2022077"]}]},{"name":"National Key Research and Development Program of China","award":["2021YFA1301900"],"award-info":[{"award-number":["2021YFA1301900"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22007092"],"award-info":[{"award-number":["22007092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,10,8]]},"abstract":"<jats:p>\n                    As a major class of biomolecules, carbohydrates play indispensable roles in various biological processes. However, it remains largely unknown how carbohydrates directly modulate important drug targets, such as G-protein coupled receptors (GPCRs). Here, we employed P2Y purinoceptor 14 (P2Y14), a drug target for inflammation and immune responses, to uncover the sugar nucleotide activation of GPCRs. Integrating molecular dynamics simulation with functional study, we identified the uridine diphosphate (UDP)-sugar-binding site on P2Y14, and revealed that a UDP-glucose might activate the receptor by bridging the transmembrane (TM) helices 2 and 7. Between TM2 and TM7 of P2Y14, a conserved salt bridging chain (K\n                    <jats:sup>2.60<\/jats:sup>\n                    -D\n                    <jats:sup>2.64<\/jats:sup>\n                    -K\n                    <jats:sup>7.35<\/jats:sup>\n                    -E\n                    <jats:sup>7.36<\/jats:sup>\n                    [KDKE]) was identified to distinguish different UDP-sugars, including UDP-glucose, UDP-galactose, UDP-glucuronic acid, and UDP-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosamine. We identified the KDKE chain as a conserved functional motif of sugar binding for both P2Y14 and P2Y purinoceptor 12 (P2Y12), and then designed three sugar nucleotides as agonists of P2Y12. These results not only expand our understanding for activation of purinergic receptors but also provide insights for the carbohydrate drug development for GPCRs.\n                  <\/jats:p>","DOI":"10.7554\/elife.85449","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T04:04:01Z","timestamp":1696824241000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85449","source":"Crossref","is-referenced-by-count":8,"title":["Identification of a carbohydrate recognition motif of purinergic receptors"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4158-790X","authenticated-orcid":true,"given":"Lifen","family":"Zhao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022syn853","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Drug Research, Carbohydrate-Based Drug Research Center and National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of 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