Fusobacterium nucleatum Lipopolysaccharides O-Antigen Defines a Novel Siglec-7 Binding Epitope

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F25%3A10507443" target="_blank" >RIV/00216208:11310/25:10507443 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Phoe9n047u" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Phoe9n047u</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacsau.5c00810" target="_blank" >10.1021/jacsau.5c00810</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Fusobacterium nucleatum Lipopolysaccharides O-Antigen Defines a Novel Siglec-7 Binding Epitope

Popis výsledku v původním jazyce

Fusobacterium nucleatum (Fn) is a Gram-negative bacterium predominantly found in the human oral cavity, occasionally linked to systemic diseases, including colorectal cancer. Bacterial lipopolysaccharides (LPSs) represent one of the possible virulence factors contributing to and promoting disease progression. Fn LPS is recognized by Siglec-7, a sialic acid-binding inhibitory receptor expressed on immune cells and promising novel target for cancer immunotherapy. Through a combined approach of structural biology, biophysics, NMR, and computational methods, we explored the molecular basis of the interaction between Siglec-7 and the LPS fromF. nucleatum ssp polymorphum 10953, whose O-antigen contains peculiar sugars such as the neuraminic acid and the AAT (FucpNAc4N). We discovered a novel Siglec-7 binding epitope within the LPS O-antigen repeating unit, defined by its internal sialic acid and AAT residues. We propose a wing-like movement of the O-antigen, where Siglec-7 BC and CC&apos; loops alternately engage the O-antigen edges within the binding site, with the BC loop forming more stable interactions. We uncover a novel Fn10953 immune evasion mechanism and highlight Siglec-7 and LPS as novel therapeutic targets for Fn-associated CRC, providing new avenues for intervention.

Název v anglickém jazyce

Fusobacterium nucleatum Lipopolysaccharides O-Antigen Defines a Novel Siglec-7 Binding Epitope

Popis výsledku anglicky

Fusobacterium nucleatum (Fn) is a Gram-negative bacterium predominantly found in the human oral cavity, occasionally linked to systemic diseases, including colorectal cancer. Bacterial lipopolysaccharides (LPSs) represent one of the possible virulence factors contributing to and promoting disease progression. Fn LPS is recognized by Siglec-7, a sialic acid-binding inhibitory receptor expressed on immune cells and promising novel target for cancer immunotherapy. Through a combined approach of structural biology, biophysics, NMR, and computational methods, we explored the molecular basis of the interaction between Siglec-7 and the LPS fromF. nucleatum ssp polymorphum 10953, whose O-antigen contains peculiar sugars such as the neuraminic acid and the AAT (FucpNAc4N). We discovered a novel Siglec-7 binding epitope within the LPS O-antigen repeating unit, defined by its internal sialic acid and AAT residues. We propose a wing-like movement of the O-antigen, where Siglec-7 BC and CC&apos; loops alternately engage the O-antigen edges within the binding site, with the BC loop forming more stable interactions. We uncover a novel Fn10953 immune evasion mechanism and highlight Siglec-7 and LPS as novel therapeutic targets for Fn-associated CRC, providing new avenues for intervention.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JACS Au

ISSN

2691-3704

e-ISSN

2691-3704

Svazek periodika

5

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

5367-5380

Kód UT WoS článku

001579189200001

EID výsledku v databázi Scopus

2-s2.0-105022798795