9Z76

Cryo-EM structure of Enterotoxigenic Escherichia coli autotransporter A (EatA) complexed with the fragment antigen binding domain of monoclonal antibody 25

Summary for 9Z76

• Entry DOI: 10.2210/pdb9z76/pdb
• EMDB information: 73869
• Descriptor: Serine protease EatA, Heavy chain of the fragment antigen binding domain of monoclonal antibody 25, Light chain of the fragment antigen binding domain of monoclonal antibody 25 (3 entities in total)
• Functional Keywords: protease, beta-helix, secreted, monoclonal antibody, hydrolase, hydrolase-immune system complex, hydrolase/immune system
• Biological source: Escherichia coli; More
• Total number of polymer chains: 3
• Total formula weight: 158422.32

Authors

Buckley, D.P.,Berndsen, Z.T. (deposition date: 2025-11-16, release date: 2026-06-03, Last modification date: 2026-07-01)

Primary citation

Buckley, D.P.,Akhtar, M.,Thapa, M.,Schmitz, A.,Turner, J.,Vickers, T.J.,Khatoon, N.,Kaisar, M.H.,Coggin, J.A.,Ganguli, D.,Sheikh, A.,Laird, R.M.,Poly, F.,Porter, C.K.,Ruiz-Perez, F.,Miller, M.J.,Chowdhury, F.,Bhuiyan, T.R.,Qadri, F.,Trillo-Muyo, S.,Dolan, B.,van der Post, S.,Ellebedy, A.,Berndsen, Z.T.,Fleckenstein, J.M.
Human enterotoxigenic Escherichia coli (ETEC) infections elicit antibodies that broadly neutralize mucinases of pathogenic Escherichia coli and Shigella.
Proc.Natl.Acad.Sci.USA, 123:e2614012123-e2614012123, 2026

PubMed Abstract: Enterotoxigenic (ETEC) and are the most common bacterial diarrheal pathogens among young children of low-middle income regions. Enteric pathogens must overcome formidable host defenses, including the protective barrier formed by intestinal mucus. ETEC produce a virulence protein called EatA, a member of the Serine Protease Autotransporter of the (SPATE) family, where the secreted passenger domain (EatA) specifically degrades MUC2, the major mucus secreted by goblet cells of the human intestine. Notably, some spp., as well as other diarrheagenic pathovars, secrete homologues of EatA known as SepA, and Pic. Here, we demonstrate that EatA, SepA, and Pic are functionally redundant MUC2 mucinases and that recombinant monoclonal antibodies (mAbs) derived from plasmablasts of ETEC-infected humans can inhibit MUC2 degradation by all three proteases. We present cryo-EM structures of EatA and the related SPATE proteins, SepA, and Pic, complexed to fragment antigen-binding portions of these mAbs to demonstrate that those targeting a core β-helix epitope shared by all three SPATE molecules broadly neutralize the capacity to degrade MUC2. These mAbs effectively prevent MUC2 degradation by each SPATE as well as mucus penetration by ETEC, , and Pic-producing enteroaggregative (EAEC). We anticipate that these studies could facilitate rational design of vaccines that broadly protect against major enteric pathogens by targeting a shared virulence feature.

PubMed: 42296351
DOI: 10.1073/pnas.2614012123

Experimental method

ELECTRON MICROSCOPY (3.32 Å)