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TitleStructural Basis of Shiga Toxin Neutralization by Human Antibodies Targeting Canonical Receptor-Binding and Non-Canonical Assembly Sites.
Journal, issue, pagesAdv Sci (Weinh), Page e77402, Year 2026
Publish dateAug 30, 2026
AuthorsJianting Ke / Xin Li / Xiaoli Wang / Zhaoxia Huang / Shaojie Xue / Yuyang Liu / Jing Pan / Guowei Hu / Yayu Wang / Cheng Wang / Shoudeng Chen /
PubMed AbstractShiga toxin-producing Escherichia coli (STEC) infections cause severe systemic complications, yet targeted antitoxin therapeutics remain an unmet clinical need. Here, we isolated a panel of human ...Shiga toxin-producing Escherichia coli (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-electron microscopy structure of the human mAb RDS059 in complex with the Shiga toxin 1a B subunit (Stx1aB) reveals that RDS059 recognizes the surface-exposed loop of Stx1aB, whereby it directly competes with the host glycolipid globotriaosylceramide (Gb3) to block toxin-cell engagement. In contrast, RDS045 binds a non-canonical quaternary epitope at the pentameric interface of Stx1aB, acting as an interprotomer clamp via an extensive hydrogen-bonding and cation-π 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.
External linksAdv Sci (Weinh) / PubMed:42669652 / PubMed Central
MethodsEM (single particle)
Resolution2.0 - 2.5 Å
Structure data

80320

25rg

EMDB-80320, PDB-25rg:
CyroEM structure of the complex between Shiga toxin Stx1a B subunit and neutralising Fab fragment of RDS045
Method: EM (single particle) / Resolution: 2.5 Å

80337

25sb

EMDB-80337, PDB-25sb:
CyroEM structure of the complex between Shiga toxin Stx1a B subunit and neutralising Fab fragment of RDS059
Method: EM (single particle) / Resolution: 2.0 Å

Source
  • homo sapiens (human)
  • shigella dysenteriae (bacteria)
  • escherichia coli o157:h7 (bacteria)
KeywordsTOXIN/IMMUNE SYSTEM / Shiga toxin B subunit / Antibody / TOXIN-IMMUNE SYSTEM complex / Shiga toxin / B subunit

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