{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:57:19Z","timestamp":1766138239904,"version":"3.40.5"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201019\u2010CE17\u20100021"],"award-info":[{"award-number":["ANR\u201019\u2010CE17\u20100021"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Protein\u2013protein interactions (PPIs) are attractive targets as they are critical in a variety of biological processes and pathologies. As an illustration, the interleukin 3 (IL\u20103) and its \u03b1 subunit receptor (IL\u20103R\u03b1) are two proteins belonging to the cytokine or receptor \u03b2c family and are involved in several disorders like inflammatory diseases or hematological malignancies. This PPI exhibits a low binding affinity and a complex formed by a mutant form of IL\u20103 (superkine) and IL\u20103R\u03b1 have emerged from the literature, with an increase of the affinity. Therefore, in this study, we performed molecular dynamics simulations and binding energy calculation in order to evaluate protein dynamics and to characterize the main interactions between IL\u20103 and IL\u20103R\u03b1, considering both wild\u2010type and mutant. First, in the case of IL\u20103R\u03b1\/IL\u20103 wild\u2010type complex, IL\u20103R\u03b1 can adopt three different conformations essentially driven by NTD domain, including the open and closed conformations, previously observed in crystal structures. Additionally, our results reveal a third conformation that has a distinct interaction profile that the others. Interestingly, these conformational changes are attenuated in IL\u20103R\u03b1\/IL\u20103 mutant complex. Then, we highlighted the contribution of different residues which interact principally with IL\u20103 or IL\u20103R\u03b1 conserved region. As for the mutated residue at position 135 of IL\u20103, other residues such as IL\u20103 E138, IL\u20103 D40, IL\u20103R\u03b1 Y279, IL\u20103R\u03b1 K235, or IL\u20103R\u03b1 R277 seem important for a low or a high binding affinity. Altogether these findings yield new information that could be exploited in a drug discovery process.<\/jats:p>","DOI":"10.1002\/prot.26476","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T16:02:16Z","timestamp":1675353736000},"page":"904-919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Conformational and binding mode assessment of the human IL\u20103 recognition by its alpha receptor"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-544X","authenticated-orcid":false,"given":"Jade","family":"Fogha","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 des Antilles and Universit\u00e9 de la R\u00e9union, INSERM, Biologie Int\u00e9gr\u00e9e du Globule Rouge, UMR_S 1134, DSIMB  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-5626","authenticated-orcid":false,"given":"Alexandre G.","family":"de Brevern","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 des Antilles and Universit\u00e9 de la R\u00e9union, INSERM, Biologie Int\u00e9gr\u00e9e du Globule Rouge, UMR_S 1134, DSIMB  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6400-927X","authenticated-orcid":false,"given":"Julien","family":"Diharce","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 des Antilles and Universit\u00e9 de la R\u00e9union, INSERM, Biologie Int\u00e9gr\u00e9e du Globule Rouge, UMR_S 1134, DSIMB  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_11_2_1","DOI":"10.1016\/0192\u20100561(92)90172\u2010H"},{"doi-asserted-by":"publisher","key":"e_1_2_11_3_1","DOI":"10.1111\/j.1398\u20109995.2004.00606.x"},{"doi-asserted-by":"publisher","key":"e_1_2_11_4_1","DOI":"10.1016\/j.cytogfr.2013.03.002"},{"doi-asserted-by":"publisher","key":"e_1_2_11_5_1","DOI":"10.1371\/journal.pone.0050375"},{"doi-asserted-by":"publisher","key":"e_1_2_11_6_1","DOI":"10.1016\/0092\u20108674(91)90039\u20102"},{"doi-asserted-by":"publisher","key":"e_1_2_11_7_1","DOI":"10.1002\/iub.350"},{"doi-asserted-by":"publisher","key":"e_1_2_11_8_1","DOI":"10.1146\/annurev.immunol.24.021605.090616"},{"doi-asserted-by":"publisher","key":"e_1_2_11_9_1","DOI":"10.1016\/j.cyto.2015.02.005"},{"doi-asserted-by":"publisher","key":"e_1_2_11_10_1","DOI":"10.1038\/s41467\u2010017\u201002633\u20107"},{"doi-asserted-by":"publisher","key":"e_1_2_11_11_1","DOI":"10.1073\/pnas.89.24.11842"},{"doi-asserted-by":"publisher","key":"e_1_2_11_12_1","DOI":"10.1074\/jbc.272.36.22630"},{"doi-asserted-by":"publisher","key":"e_1_2_11_13_1","DOI":"10.1101\/cshperspect.a028514"},{"doi-asserted-by":"publisher","key":"e_1_2_11_14_1","DOI":"10.3390\/ijms20040834"},{"doi-asserted-by":"publisher","key":"e_1_2_11_15_1","DOI":"10.1016\/j.smim.2021.101510"},{"doi-asserted-by":"publisher","key":"e_1_2_11_16_1","DOI":"10.3390\/cancers11091358"},{"doi-asserted-by":"publisher","key":"e_1_2_11_17_1","DOI":"10.1126\/science.aaa4268"},{"doi-asserted-by":"publisher","key":"e_1_2_11_18_1","DOI":"10.1016\/j.jaci.2013.07.046"},{"doi-asserted-by":"publisher","key":"e_1_2_11_19_1","DOI":"10.4049\/JIMMUNOL.0801782"},{"doi-asserted-by":"publisher","key":"e_1_2_11_20_1","DOI":"10.1016\/j.celrep.2014.06.038"},{"doi-asserted-by":"publisher","key":"e_1_2_11_21_1","DOI":"10.1021\/bi101810f"},{"doi-asserted-by":"publisher","key":"e_1_2_11_22_1","DOI":"10.1016\/j.str.2011.08.015"},{"doi-asserted-by":"publisher","key":"e_1_2_11_23_1","DOI":"10.1016\/j.str.2016.05.017"},{"doi-asserted-by":"publisher","key":"e_1_2_11_24_1","DOI":"10.1007\/s00726\u2010021\u201003026\u20103"},{"doi-asserted-by":"publisher","key":"e_1_2_11_25_1","DOI":"10.1006\/jmbi.1996.0337"},{"doi-asserted-by":"publisher","key":"e_1_2_11_26_1","DOI":"10.1093\/nar\/28.1.235"},{"doi-asserted-by":"publisher","key":"e_1_2_11_27_1","DOI":"10.1002\/prot.22488"},{"unstructured":"Schr\u00f6dinger L. 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