PXD057683

PXD057683 is an original dataset announced via ProteomeXchange.

Title	Antibodies disrupt bacterial adhesion by ligand mimicry and allostery
Description	Many microorganisms attach to host cells using lectins that bind surface glycans, a critical step in infections that makes lectins promising antimicrobial targets. FimH, the adhesin on Type 1 E. coli fimbriae, is a lectin that specifically binds the terminal mannose in glycans on the surfaces of host cells. Upon glycan binding, FimH transitions from the low affinity conformation to a high affinity conformation that can act as a catch-bond. Previous studies generated a polyclonal antibody response against FimH, where monoclonal antibodies from the pool targets different epitopes, including the glycan-binding pocket and key allosteric sites. However, the effector mechanisms of these antibodies remain unclear. Here, we use cryoEM paired with mass spectrometry, binding assays, and molecular dynamics simulations to determine the structure-function relationships underlying antibody-FimH binding. Our study reveals four distinct antibody mechanisms: ligand mimicry by an N-linked glycan on the antibody, direct occlusion of the open ligand pocket, FimH conformational arrest, and ligand trapping through long-range allosteric effects. Incorporation of antibody glycans into the antigen binding interface to mimic native ligands may be a general strategy for targeting lectins involved in host attachment. These structures reveal multiple mechanisms of host antibody responses to an allosteric protein, and provide blueprints for new antimicrobials against adhesins.
HostingRepository	PRIDE
AnnounceDate	2025-10-29
AnnouncementXML	Submission_2025-10-29_09:00:46.970.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tim S Veth
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	complex glycosylation
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-08 14:46:05	ID requested
⏵ 1	2025-10-29 09:00:47	announced

10.1038/S41467-025-65666-3;

submitter keyword: Antibodies

FimH

Bacterial adhesion

Fab

Glycosylation

Cyo-EM

Mass spectrometry

Nicholas M Riley
contact affiliation	Department of Chemistry, University of Washington, Seattle, WA
contact email	nmriley@uw.edu
lab head
Tim S Veth
contact affiliation	University of Washington
contact email	tveth@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057683
     1. Label: PRIDE project
     2. Name: Antibodies disrupt bacterial adhesion by ligand mimicry and allostery