
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.12.611726
preprint
1
Article
Biantennary N-glycans As Receptors for MARTX Toxins in Vibrio Pathogenesis
Chen Jiexi http://orcid.org/0000-0003-2243-2384

Goerdeler Felix http://orcid.org/0000-0002-7190-9145

Jaroentomeechai Thapakorn http://orcid.org/0000-0003-2235-7820

Hernandez Francisco X. S.
Wang Xiaozhong http://orcid.org/0000-0003-0219-0752

Clausen Henrik http://orcid.org/0000-0002-0915-5055

Narimatsu Yoshiki http://orcid.org/0000-0003-1428-5695

Satchell Karla J. F. http://orcid.org/0000-0003-3274-7611

12 9 2024
2024.09.12.611726https://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.12.611726
nihpp-2024.09.12.611726.pdf
ABSTRACT

Multifunctional Autoprocessing Repeats-in-Toxin (MARTX) toxins are a diverse effector delivery platform of many Gram-negative bacteria that infect mammals, insects, and aquatic animal hosts. The mechanisms by which these toxins recognize host cell receptors for translocation of toxic effectors into the cell have remained elusive. Here, we map the first surface receptor-binding domain of a MARTX toxin from the highly lethal foodborne pathogen Vibrio vulnificus . This domain corresponds to a 273-amino acid sequence with predicted symmetrical immunoglobulin-like folds. We demonstrate that this domain binds internal N -acetylglucosamine on complex biantennary N-glycans with select preference for L1CAM and other N-glycoproteins with multiple N-glycans on host cell surfaces. This receptor binding domain is essential for V. vulnificus pathogenesis during intestinal infection. The identification of a highly conserved motif universally present as part of all N-glycans correlates with the V. vulnificus MARTX toxin boasting broad specificity and targeting nearly all cell types.
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