7K7H

Density-fitted Model Structure of Antibody Variable Domains of TyTx1 in Complex with PltB pentamer of Typhoid Toxin

Summary for 7K7H

• Entry DOI: 10.2210/pdb7k7h/pdb
• EMDB information: 22699
• Descriptor: Pertussis like toxin subunit B, Fab Light Chain Variable Domain, Fab Heavy Chain Variable Domain, ... (4 entities in total)
• Functional Keywords: typhoid toxin, a2b5, antibody, fab, toxin
• Biological source: Salmonella enterica subsp. enterica serovar Typhi str. CT18; More
• Total number of polymer chains: 8
• Total formula weight: 89962.71

Authors

Nguyen, T.,Feathers, J.R.,Fromme, J.C.,Song, J. (deposition date: 2020-09-22, release date: 2021-09-01, Last modification date: 2021-09-22)

Primary citation

Nguyen, T.,Richards, A.F.,Neupane, D.P.,Feathers, J.R.,Yang, Y.A.,Sim, J.H.,Byun, H.,Lee, S.,Ahn, C.,Van Slyke, G.,Fromme, J.C.,Mantis, N.J.,Song, J.
The structural basis of Salmonella A 2 B 5 toxin neutralization by antibodies targeting the glycan-receptor binding subunits.
Cell Rep, 36:109654-109654, 2021

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 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.

PubMed: 34496256
DOI: 10.1016/j.celrep.2021.109654

Experimental method

ELECTRON MICROSCOPY (3 Å)