{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:13:02Z","timestamp":1789776782717,"version":"4.0.1"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0906003"],"award-info":[{"award-number":["2019YFA0906003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["GXWD20201231105722002- 20200831175432002"],"award-info":[{"award-number":["GXWD20201231105722002- 20200831175432002"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070950"],"award-info":[{"award-number":["32070950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M713049"],"award-info":[{"award-number":["2022M713049"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Municipal Science and Technology Innovation Council | Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["RCBS20221008093330067"],"award-info":[{"award-number":["RCBS20221008093330067"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,6,4]]},"abstract":"<jats:p>\n                    Essential for reactive oxygen species (EROS) protein is a recently identified molecular chaperone of NOX2 (gp91\n                    <jats:sup>phox<\/jats:sup>\n                    ), the catalytic subunit of phagocyte NADPH oxidase. Deficiency in EROS is a recently identified cause for chronic granulomatous disease, a genetic disorder with recurrent bacterial and fungal infections. Here, we report a cryo-EM structure of the EROS\u2013NOX2\u2013p22\n                    <jats:sup>phox<\/jats:sup>\n                    heterotrimeric complex at an overall resolution of 3.56\u00c5. EROS and p22\n                    <jats:sup>phox<\/jats:sup>\n                    are situated on the opposite sides of NOX2, and there is no direct contact between them. EROS associates with NOX2 through two antiparallel transmembrane (TM) \u03b1-helices and multiple \u03b2-strands that form hydrogen bonds with the cytoplasmic domain of NOX2. EROS binding induces a 79\u00b0 upward bend of TM2 and a 48\u00b0 backward rotation of the lower part of TM6 in NOX2, resulting in an increase in the distance between the two hemes and a shift of the binding site for flavin adenine dinucleotide (FAD). These conformational changes are expected to compromise superoxide production by NOX2, suggesting that the EROS-bound NOX2 is in a protected state against activation. Phorbol myristate acetate, an activator of NOX2 in vitro, is able to induce dissociation of NOX2 from EROS with concurrent increase in FAD binding and superoxide production in a transfected COS-7 model. In differentiated neutrophil-like HL-60, the majority of NOX2 on the cell surface is dissociated with EROS. Further studies are required to delineate how EROS dissociates from NOX2 during its transport to cell surface, which may be a potential mechanism for regulation of NOX2 activation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2320388121","type":"journal-article","created":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T12:00:39Z","timestamp":1717329639000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0261-3727","authenticated-orcid":false,"given":"Shiyu","family":"Liang","sequence":"first","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"},{"name":"Dongguan Songshan Lake Central Hospital, Dongguan Third People\u2019s Hospital, Dongguan, Guangdong 523326, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-8260","authenticated-orcid":false,"given":"Yezhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"},{"name":"Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen 518132, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0812-183X","authenticated-orcid":false,"given":"Fuxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youli","family":"Zhou","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7909-3230","authenticated-orcid":false,"given":"Yuanzhengyang","family":"Long","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen 518132, China"},{"name":"Key Laboratory of Computational Chemistry and Drug Design, Peking University Shenzhen Graduate School, Nanshan District, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3538-9349","authenticated-orcid":false,"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4517-7216","authenticated-orcid":false,"given":"Ruobing","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2164-5620","authenticated-orcid":false,"given":"Richard D.","family":"Ye","sequence":"additional","affiliation":[{"name":"Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China"},{"name":"The Chinese University of Hong Kong, Shenzhen Futian Biomedical Innovation R&amp;D Center, Shenzhen, Guangdong 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.89"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2012.11.002"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(93)90051-N"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2003.12.001"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2021.102587"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060890"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/276515a0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-004-0679-8"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01658-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","unstructured":"E. Pick \u201cParadigm shifts in the history of Nox2 and its regulators: An appreciative critique\u201d in NADPH Oxidases Revisited: From Function to Structure (2023) pp. 3\u201363 10.1007\/978-3-031-23752-2_1. 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Y. Liang A. J. Liu Y. Z. Liu Cryo-EM structure of NADPH oxidase 2 in complex with p22phox and EROS. Protein Data Bank. https:\/\/www.rcsb.org\/structure\/8KEI. Deposited 11 August 2023.","DOI":"10.2210\/pdb8kei\/pdb"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2320388121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T12:03:31Z","timestamp":1717329811000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2320388121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,28]]},"references-count":42,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,6,4]]}},"alternative-id":["10.1073\/pnas.2320388121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2320388121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,28]]},"assertion":[{"value":"2023-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2320388121"}}