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

Result code in 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>
Result on the web
<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>

Result language
angličtina
Original language name
Fusobacterium nucleatum Lipopolysaccharides O-Antigen Defines a Novel Siglec-7 Binding Epitope
Original language description
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' 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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