{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:35Z","timestamp":1786951535738,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","award":["2018\u201004969 2019\u201002496"],"award-info":[{"award-number":["2018\u201004969 2019\u201002496"]}],"id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    The glutamate delta receptors GluD1 and GluD2 are part of the ionotropic glutamate receptor (iGluR) family; however, delta receptors differ from other iGluRs as they do not bind glutamate. These receptors have important and diverse functions in the brain and are known to be involved in various neurological diseases. Here, we report the monomeric X\u2010ray crystal structure of the ligand\u2010binding domain of rat GluD1 (rGluD1\u2010LBD) with D\u2010serine and Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ions, determined at 2.8\u2009\u00c5 resolution. By comparing the structures with Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ions (rGluD1\u2010LBD) and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ions (human, hGluD1\u2010LBD), we show that species and crystallization differences do not affect intermediate domain closure and D\u2010serine interactions with GluD1. Furthermore, examining the effect of replacing the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ions in the hGluD1\u2010LBD dimer with Mg\n                    <jats:sup>2+<\/jats:sup>\n                    , Zn\n                    <jats:sup>2+<\/jats:sup>\n                    or Na\n                    <jats:sup>+<\/jats:sup>\n                    ions did not reveal significant differences in the overall structure of the hGluD1\u2010LBD for the different cations. We show that the cations were coordinated by the same residues, Glu527, Val530 and Asp531, and several water molecules. In the structure of hGluD1\u2010LBD, Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ions are present at the dimer interface and molecular dynamics (MD) simulations showed that removal of the ions leads to opening of the dimer, highlighting the importance of Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ions in stabilizing the dimer. Finally, MD simulations of hGluD1\u2010LBD and the Pro725 to Ser725 mutant, with and without D\u2010serine in the binding site, suggest that Pro725 hinders full domain closure in GluD1, whereas an apparent synergistic effect of D\u2010serine and mutation to Ser725 leads to a significant interlobe closure of the clamshell\u2010like structure.\n                  <\/jats:p>","DOI":"10.1111\/febs.70702","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:55:32Z","timestamp":1786949732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ion binding sites and intermediate domain closure induced by D\u2010serine in the\n                    <scp>GluD1<\/scp>\n                    ligand\u2010binding domain"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-2998","authenticated-orcid":false,"given":"Flemming Steen","family":"J\u00f8rgensen","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma Grosvald","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla A.","family":"Frydenvang","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2654-1510","authenticated-orcid":false,"given":"Jette Sandholm","family":"Kastrup","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108683"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.70415"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81186-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-019-0359-y"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf3406"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2023.05.012"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2016.12.004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0827-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0628-14.2014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02051-06"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.09.027"},{"key":"e_1_2_10_13_1","first-page":"E5373","article-title":"Postsynaptic 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