Multiple O-and an N-glycosylation of the stalk region of the NK cell activation receptor NKp46 mediates its interaction with the Candida glabrata epithelial adhesin 1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00619611" target="_blank" >RIV/86652036:_____/25:00619611 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10500804

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0141813025035895?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0141813025035895?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijbiomac.2025.143037" target="_blank" >10.1016/j.ijbiomac.2025.143037</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Multiple O-and an N-glycosylation of the stalk region of the NK cell activation receptor NKp46 mediates its interaction with the Candida glabrata epithelial adhesin 1

Popis výsledku v původním jazyce

Natural killer (NK) cells are critical components of the innate immune system. Their primary role is to induce apoptosis in target cells, such as cancerous or virally infected cells. These targets are recognized through interactions between activating or inhibitory receptors on the NK cell surface. Among the activating receptors is the natural cytotoxicity receptor NKp46. Several ligands for this receptor have been identified, including the epithelial adhesin Epa1 from the yeast Candida glabrata. Invasive candidiasis caused by this yeast is a significant complication for patients with hematological diseases. The interaction between NKp46 and Epa1 is thought to depend specifically on an O-glycan at threonine 225 of NKp46. To elucidate the molecular details of this interaction, we optimized the recombinant production of soluble NKp46 and Epa1, generated glycosylation variants of multiple NKp46 mutants, and evaluated the role of NKp46 glycosylation in Epa1 binding using microscale thermophoresis and isothermal titration calorimetry. Additionally, for the first time, we provide a comprehensive glycosylation profile of NKp46, determined through mass spectrometry of intact glycopeptides obtained by O-glycoprotease and trypsin proteolysis. Our findings demonstrate that the NKp46 stalk is glycosylated at multiple sites, involving both an N-glycan and more than one O-glycan. These glycans are critical for the interaction with Epa1, providing NK cells with enhanced sensitivity to Candida glabrata epitopes.

Název v anglickém jazyce

Multiple O-and an N-glycosylation of the stalk region of the NK cell activation receptor NKp46 mediates its interaction with the Candida glabrata epithelial adhesin 1

Popis výsledku anglicky

Natural killer (NK) cells are critical components of the innate immune system. Their primary role is to induce apoptosis in target cells, such as cancerous or virally infected cells. These targets are recognized through interactions between activating or inhibitory receptors on the NK cell surface. Among the activating receptors is the natural cytotoxicity receptor NKp46. Several ligands for this receptor have been identified, including the epithelial adhesin Epa1 from the yeast Candida glabrata. Invasive candidiasis caused by this yeast is a significant complication for patients with hematological diseases. The interaction between NKp46 and Epa1 is thought to depend specifically on an O-glycan at threonine 225 of NKp46. To elucidate the molecular details of this interaction, we optimized the recombinant production of soluble NKp46 and Epa1, generated glycosylation variants of multiple NKp46 mutants, and evaluated the role of NKp46 glycosylation in Epa1 binding using microscale thermophoresis and isothermal titration calorimetry. Additionally, for the first time, we provide a comprehensive glycosylation profile of NKp46, determined through mass spectrometry of intact glycopeptides obtained by O-glycoprotease and trypsin proteolysis. Our findings demonstrate that the NKp46 stalk is glycosylated at multiple sites, involving both an N-glycan and more than one O-glycan. These glycans are critical for the interaction with Epa1, providing NK cells with enhanced sensitivity to Candida glabrata epitopes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

International Journal of Biological Macromolecules

ISSN

0141-8130

e-ISSN

1879-0003

Svazek periodika

310

Číslo periodika v rámci svazku

MAY 2025

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

143037

Kód UT WoS článku

001477216100001

EID výsledku v databázi Scopus

2-s2.0-105002904761