4iop
From Proteopedia
Crystal structure of NKp65 bound to its ligand KACL
Structural highlights
Function[CLC2A_HUMAN] Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity.[1] [2] [KLRF2_HUMAN] C-type lectin-like receptor involved in natural killer cell mediated cytotoxicity and cytokine secretion in keratinocytes via its interaction with CLEC2A. Publication Abstract from PubMedThe 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 x 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. Structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex.,Li Y, Wang Q, Chen S, Brown PH, Mariuzza RA Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11505-10. doi:, 10.1073/pnas.1303300110. Epub 2013 Jun 26. PMID:23803857[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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