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Natural Killer Cell Activation Receptor NKp30 Oligomerization Depends on Its N-Glycosylation

O. Skořepa, S. Pazicky, B. Kalousková, J. Bláha, C. Abreu, T. Ječmen, M. Rosůlek, A. Fish, A. Sedivy, K. Harlos, J. Dohnálek, T. Skálová, O. Vaněk,

. 2020 ; 12 (7) : . [pub] 20200721

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc20021946

Grantová podpora
18-10687S Grantová Agentura České Republiky
LTC17065 Ministerstvo Školství, Mládeže a Tělovýchovy
CZ.02.1.01/0.0/0.0/16_013/0001776 Ministerstvo Školství, Mládeže a Tělovýchovy
CZ.1.05/1.1.00/02.0109 European Regional Development Fund
927916 Grantová Agentura, Univerzita Karlova
SVV 260427/2020 Univerzita Karlova v Praze
LM2015043 Ministerstvo Školství, Mládeže a Tělovýchovy
203141/Z/16/Z Wellcome Trust - United Kingdom
CA15126 European Cooperation in Science and Technology

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 of N-glycosylation. In this study, we assessed whether NKp30 oligomerization depends on its N-glycosylation. Our results show that NKp30 forms oligomers when expressed in HEK293S GnTI- cell lines with simple N-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.

Citace poskytuje Crossref.org

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