3CII

Structure of NKG2A/CD94 bound to HLA-E

Summary for 3CII

• Entry DOI: 10.2210/pdb3cii/pdb
• Descriptor: HLA class I histocompatibility antigen, alpha chain E, Beta-2-microglobulin, HLA class I histocompatibility antigen peptide, ... (5 entities in total)
• Functional Keywords: c-type lectin-like, glycoprotein, immune response, membrane, mhc i, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, lectin, receptor, signal-anchor, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P13747 P17693; Secreted: P61769; Membrane; Single-pass type II membrane protein: Q13241 P26715
• Total number of polymer chains: 10
• Total formula weight: 145073.39

Authors

Strong, R.K.,Kaiser, B.K.,Pizarro, J.C. (deposition date: 2008-03-11, release date: 2008-05-13, Last modification date: 2024-11-20)

Primary citation

Kaiser, B.K.,Pizarro, J.C.,Kerns, J.,Strong, R.K.
Structural basis for NKG2A/CD94 recognition of HLA-E.
Proc.Natl.Acad.Sci.Usa, 105:6696-6701, 2008

PubMed Abstract: The NKG2x/CD94 (x = A, C, E) natural killer-cell receptors perform an important role in immunosurveillance by binding to HLA-E complexes that exclusively present peptides derived from MHC class I leader sequences, thereby monitoring MHC class I expression. We have determined the crystal structure of the NKG2A/CD94/HLA-E complex at 4.4-A resolution, revealing two critical aspects of this interaction. First, the C-terminal region of the peptide, which displays the most variability among class I leader sequences, interacts entirely with CD94, the invariant component of these receptors. Second, residues 167-170 of NKG2A/C account for the approximately 6-fold-higher affinity of the inhibitory NKG2A/CD94 receptor compared to its activating NKG2C/CD94 counterpart. These residues do not contact HLA-E or peptide directly but instead form part of the heterodimer interface with CD94. An evolutionary analysis across primates reveals that whereas CD94 is evolving under purifying selection, both NKG2A and NKG2C are evolving under positive selection. Specifically, residues at the CD94 interface have evolved under positive selection, suggesting that the evolution of these genes is driven by an interaction with pathogen-derived ligands. Consistent with this possibility, we show that NKG2C/CD94, but not NKG2A/CD94, weakly but specifically binds to the CMV MHC-homologue UL18. Thus, the evolution of the NKG2x/CD94 family of receptors has likely been shaped both by the need to bind the invariant HLA-E ligand and the need to avoid subversion by pathogen-derived decoys.

PubMed: 18448674
DOI: 10.1073/pnas.0802736105

Experimental method

X-RAY DIFFRACTION (4.41 Å)