Strukturní biochemie proteinu NKp80, aktivačního receptoru lidských lymfocytů

Pazderová, Kristýna

Natural Killer (NK) cells can spontaneously destroy target cells, such as infected, damaged, or malignant cells. NK cell cytotoxicity is mediated by activating receptors on their surface, such as NKp80 (Natural Killer protein 80 kDa). The human receptor NKp80 stimulates cytotoxicity through its interaction with its ligand AICL (Activation Induced C-type Lectin), which is constitutively expressed by all myeloid cells. In pathological conditions, such as cancerous or damaged cells, AICL is often upregulated, resulting in the lysis of these cells by NK cells expressing NKp80. This interaction is thus a promising immunotherapeutic target for treating myeloid leukaemia. However, the structures of both proteins have remained elusive. Therefore, we have focused on the successful production of the extracellular domain of these proteins. To improve the production yield of NKp80, we introduced a series of mutations in the stalk region to study their effect on production, stability, and homodimer formation. The introduced mutations significantly increased the production yield allowing for a large-scale production with subsequent crystallisation of the protein. The crystallisation resulted in the elucidation of the hitherto unknown structure of NKp80 homodimer at a resolution of 2.9 Å. However, the large-scale...

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