{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:14:50Z","timestamp":1788146090274,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["9256930332561143026"],"award-info":[{"award-number":["9256930332561143026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470746"],"award-info":[{"award-number":["82470746"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2025ZD01903905"],"award-info":[{"award-number":["2025ZD01903905"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Shiga toxin\u2010producing\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (STEC) infections cause severe systemic complications, yet targeted antitoxin therapeutics remain an unmet clinical need. Here, we isolated a panel of human monoclonal antibodies (mAbs) targeted at STEC toxin and characterized two potent neutralizing candidates, RDS045 and RDS059. The cryo\u2010electron microscopy structure of the human mAb RDS059 in complex with the Shiga toxin 1a B subunit (Stx1aB) reveals that RDS059 recognizes the surface\u2010exposed loop of Stx1aB, whereby it directly competes with the host glycolipid globotriaosylceramide (Gb3) to block toxin\u2010cell engagement. In contrast, RDS045 binds a non\u2010canonical quaternary epitope at the pentameric interface of Stx1aB, acting as an interprotomer clamp via an extensive hydrogen\u2010bonding and cation\u2010\u03c0 interaction network. Both antibodies confer robust protection in cellular assays and an in vivo murine Stx1a challenge model. Collectively, this work defines two distinct molecular blueprints for Shiga toxin receptor blockade and assembly interference, establishing mechanistic frameworks for the development of STEC therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/advs.77402","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:59:02Z","timestamp":1788145142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Basis of Shiga Toxin Neutralization by Human Antibodies Targeting Canonical Receptor\u2010Binding and Non\u2010Canonical Assembly Sites"],"prefix":"10.1002","author":[{"given":"Jianting","family":"Ke","sequence":"first","affiliation":[{"name":"Division of Nephrology Department of Medicine The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7257-6240","authenticated-orcid":false,"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhuhai Trinomab Pharmaceutical Co., Ltd  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojie","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayu","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhuhai Trinomab Pharmaceutical Co., Ltd  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-7954","authenticated-orcid":false,"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"},{"name":"NHC Key Laboratory of Clinical Nephrology Sun Yat\u2010Sen University  Guangzhou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7634-2141","authenticated-orcid":false,"given":"Shoudeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Experimental Research The Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"},{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development Sun Yat\u2010sen University  Guangzhou Guangdong People's Republic of China"},{"name":"Guangdong Engineering Research Center of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Engineering Technology Research Center of Molecular Imaging the Fifth Affiliated Hospital Sun Yat\u2010sen University  Zhuhai Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2279"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/313437"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11040212"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro818"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins15010010"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","unstructured":"A. R.Melton\u2010Celsa \u201cShiga Toxin (Stx) Classification Structure and Function \u201d Microbiology Spectrum2 no.4(2014): EHEC\u20130024\u20132013 https:\/\/doi.org\/10.1128\/microbiolspec.EHEC\u20100024\u20102013.","DOI":"10.1128\/microbiolspec.EHEC-0024-2013"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1988.tb13756.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi971806n"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins4090729"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(05)71144\u20102"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12020067"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x18666200220143001"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102016\u201011\u2010709865"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation\u20102016.1.217"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12890"},{"key":"e_1_2_12_17_1","unstructured":"A. R.Melton\u2010CelsaandA. D.O'Brien \u201cNew Therapeutic Developments Against Shiga Toxin\u2010Producing Escherichia Coli \u201dMicrobiology Spectrum2 no.5(2014): EHEC\u20100013\u20102013 https:\/\/doi.org\/10.1128\/microbiolspec.EHEC\u20100013\u20102013."},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012997.pub2"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31823096a8"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200006293422601"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.6.2081\u20102085.2001"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/315239"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13060416"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00022\u201015"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00343\u201009"},{"issue":"2","key":"e_1_2_12_26_1","first-page":"107","article-title":"Development of a Product Anti\u2010Shiga Toxin for Prevention of the Hemolytic Uremic Syndrome","volume":"78","author":"Hiriart Y.","year":"2018","journal-title":"Medicina"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.46185"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2009.02.014"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023036\u20109"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10030108"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.566257"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4169"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039031\u20101"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798318006551"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77402","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77402","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77402","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:59:05Z","timestamp":1788145145000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":37,"alternative-id":["10.1002\/advs.77402"],"URL":"https:\/\/doi.org\/10.1002\/advs.77402","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]},"assertion":[{"value":"2026-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77402"}}