Natural Killer Cell Activation Receptor NKp30 Oligomerization Depends on ItsN-Glycosylation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533400" target="_blank" >RIV/61388971:_____/20:00533400 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/20:00533400 RIV/00216208:11310/20:10413388

Výsledek na webu

<a href="https://www.mdpi.com/2072-6694/12/7/1998" target="_blank" >https://www.mdpi.com/2072-6694/12/7/1998</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers12071998" target="_blank" >10.3390/cancers12071998</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Natural Killer Cell Activation Receptor NKp30 Oligomerization Depends on ItsN-Glycosylation

Popis výsledku v původním jazyce

NKp30 is one of the main human natural killer (NK) cell activating receptors used in directed immunotherapy. The oligomerization of the NKp30 ligand binding domain depends on the length of the C-terminal stalk region, but our structural knowledge of NKp30 oligomerization and its role in signal transduction remains limited. Moreover, ligand binding of NKp30 is affected by the presence and type ofN-glycosylation. In this study, we assessed whether NKp30 oligomerization depends on itsN-glycosylation. Our results show that NKp30 forms oligomers when expressed in HEK293S GnTI(-)cell lines with simpleN-glycans. However, NKp30 was detected only as monomers after enzymatic deglycosylation. Furthermore, we characterized the interaction between NKp30 and its best-studied cognate ligand, B7-H6, with respect to glycosylation and oligomerization, and we solved the crystal structure of this complex with glycosylated NKp30, revealing a new glycosylation-induced mode of NKp30 dimerization. Overall, this study provides new insights into the structural basis of NKp30 oligomerization and explains how the stalk region and glycosylation of NKp30 affect its ligand affinity. This furthers our understanding of the molecular mechanisms involved in NK cell activation, which is crucial for the successful design of novel NK cell-based targeted immunotherapeutics.

Název v anglickém jazyce

Natural Killer Cell Activation Receptor NKp30 Oligomerization Depends on ItsN-Glycosylation

Popis výsledku anglicky

NKp30 is one of the main human natural killer (NK) cell activating receptors used in directed immunotherapy. The oligomerization of the NKp30 ligand binding domain depends on the length of the C-terminal stalk region, but our structural knowledge of NKp30 oligomerization and its role in signal transduction remains limited. Moreover, ligand binding of NKp30 is affected by the presence and type ofN-glycosylation. In this study, we assessed whether NKp30 oligomerization depends on itsN-glycosylation. Our results show that NKp30 forms oligomers when expressed in HEK293S GnTI(-)cell lines with simpleN-glycans. However, NKp30 was detected only as monomers after enzymatic deglycosylation. Furthermore, we characterized the interaction between NKp30 and its best-studied cognate ligand, B7-H6, with respect to glycosylation and oligomerization, and we solved the crystal structure of this complex with glycosylated NKp30, revealing a new glycosylation-induced mode of NKp30 dimerization. Overall, this study provides new insights into the structural basis of NKp30 oligomerization and explains how the stalk region and glycosylation of NKp30 affect its ligand affinity. This furthers our understanding of the molecular mechanisms involved in NK cell activation, which is crucial for the successful design of novel NK cell-based targeted immunotherapeutics.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Cancers (Basel)

ISSN

2072-6694

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

24

Strana od-do

1998

Kód UT WoS článku

000554160800001

EID výsledku v databázi Scopus

2-s2.0-85088272571