Title :
structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex
Abstract :
- The natural killer (NK) gene complex (NKC) encodes numerous C-type lectin-like receptors that govern the activity of NK cells
- Although some of these receptors (Ly49s, NKG2D , CD94 / NKG2A ) recognize MHC or MHC-like molecules, others ( Nkrp1 , NKRP1A , NKp80 , NKp65 ) instead bind C-type lectin-like ligands to which they are genetically linked in the NKC
- To understand the basis for this recognition, we determined the structure of human NKp65 , an activating receptor implicated in the immunosurveillance of skin, bound to its NKC-encoded ligand keratinocyte-associated C-type lectin ( KACL )
- Whereas KACL forms a homodimer resembling other C-type lectin-like dimers , NKp65 is monomeric
- The binding mode in the NKp65- KACL complex, in which a monomeric receptor engages a dimeric ligand, is completely distinct from those used by Ly49s, NKG2D , or CD94 / NKG2A
- The structure explains the exceptionally high affinity of the NKp65- KACL interaction compared with other cell-cell interaction pairs (KD = 6.7 × 10(-10) M), which may compensate for the monomeric nature of NKp65 to achieve cell activation
- This previously unreported structure of an NKC-encoded receptor-ligand complex, coupled with mutational analysis of the interface, establishes a docking template that is directly applicable to other genetically linked pairs in the NKC, including Nkrp1-Clr, NKRP1A- LLT1 , and NKp80- AICL
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