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-Structure paper
Title | The structural basis of Salmonella AB toxin neutralization by antibodies targeting the glycan-receptor binding subunits. |
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Journal, issue, pages | Cell Rep, Vol. 36, Issue 10, Page 109654, Year 2021 |
Publish date | Sep 7, 2021 |
Authors | Tri Nguyen / Angelene F Richards / Durga P Neupane / J Ryan Feathers / Yi-An Yang / Ji Hyun Sim / Haewon Byun / Sohyoung Lee / Changhwan Ahn / Greta Van Slyke / J Christopher Fromme / Nicholas J Mantis / Jeongmin Song / |
PubMed Abstract | Many bacterial pathogens secrete AB toxins comprising two functionally distinct yet complementary "A" and "B" subunits to benefit the pathogens during infection. The lectin-like pentameric B subunits ...Many bacterial pathogens secrete AB toxins comprising two functionally distinct yet complementary "A" and "B" subunits to benefit the pathogens during infection. The lectin-like pentameric B subunits recognize specific sets of host glycans to deliver the toxin into target host cells. Here, we offer the molecular mechanism by which neutralizing antibodies, which have the potential to bind to all glycan-receptor binding sites and thus completely inhibit toxin binding to host cells, are inhibited from exerting this action. Cryogenic electron microscopy (cryo-EM)-based analyses indicate that the skewed positioning of the toxin A subunit(s) toward one side of the toxin B pentamer inhibited neutralizing antibody binding to the laterally located epitopes, rendering some glycan-receptor binding sites that remained available for the toxin binding and endocytosis process, which is strikingly different from the counterpart antibodies recognizing the far side-located epitopes. These results highlight additional features of the toxin-antibody interactions and offer important insights into anti-toxin strategies. |
External links | Cell Rep / PubMed:34496256 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 3.13 Å |
Structure data | EMDB-22699: Structure of TyTx1 Fab in Complex with Typhoid Toxin EMDB-22700: Density of TyTx4 Fab in Complex with Typhoid Toxin |
Source |
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Keywords | TOXIN / Typhoid Toxin / A2B5 / Antibody / Fab |