Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations.
Int J Mol Sci
; 22(13)2021 Jun 22.
Article
in English
| MEDLINE | ID: covidwho-1304657
ABSTRACT
The innate immune system's natural killer (NK) cells exert their cytolytic function against a variety of pathological challenges, including tumors and virally infected cells. Their activation depends on net signaling mediated via inhibitory and activating receptors that interact with specific ligands displayed on the surfaces of target cells. The CD94/NKG2C heterodimer is one of the NK activating receptors and performs its function by interacting with the trimeric ligand comprised of the HLA-E/ß2m/nonameric peptide complex. Here, simulations of the all-atom multi-microsecond molecular dynamics in five immune complexes provide atomistic insights into the receptor-ligand molecular recognition, as well as the molecular events that facilitate the NK cell activation. We identify NKG2C, the HLA-Eα2 domain, and the nonameric peptide as the key elements involved in the molecular machinery of signal transduction via an intertwined hydrogen bond network. Overall, the study addresses the complex intricacies that are necessary to understand the mechanisms of the innate immune system.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptides
/
Histocompatibility Antigens Class I
/
Models, Molecular
/
NK Cell Lectin-Like Receptor Subfamily D
/
NK Cell Lectin-Like Receptor Subfamily C
/
Antigen-Antibody Complex
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Ijms22136670
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