PDBsum entry 3cdg

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protein ligands Protein-protein interface(s) links
Immune system PDB id
Jmol PyMol
Protein chains
273 a.a. *
100 a.a. *
123 a.a. *
116 a.a. *
120 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Human cd94/nkg2a in complex with hla-e
Structure: Hla class i histocompatibility antigen, alpha chain e. Chain: a, c. Fragment: residues in database 23-295. Synonym: mhc class i antigen e. Engineered: yes. Beta-2-microglobulin. Chain: b, d. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-e, hla-6.2, hlae. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Gene: klrd1, cd94. Gene: klrc1, nkg2a.
3.40Å     R-factor:   0.250     R-free:   0.279
Authors: E.J.Petrie,C.S.Clements,J.Lin,L.C.Sullivan,D.Johnson, T.Huyton,A.Heroux,H.L.Hoare,T.Beddoe,H.H.Reid,M.C.J.Wilce, A.G.Brooks,J.Rossjohn
Key ref: E.J.Petrie et al. (2008). CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence. J Exp Med, 205, 725-735. PubMed id: 18332182
26-Feb-08     Release date:   22-Apr-08    
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Protein chains
Pfam   ArchSchema ?
P13747  (HLAE_HUMAN) -  HLA class I histocompatibility antigen, alpha chain E
358 a.a.
273 a.a.
Protein chains
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin
119 a.a.
100 a.a.*
Protein chains
Pfam   ArchSchema ?
Q13241  (KLRD1_HUMAN) -  Natural killer cells antigen CD94
179 a.a.
123 a.a.
Protein chain
Pfam   ArchSchema ?
P26715  (NKG2A_HUMAN) -  NKG2-A/NKG2-B type II integral membrane protein
233 a.a.
116 a.a.
Protein chain
Pfam   ArchSchema ?
P26715  (NKG2A_HUMAN) -  NKG2-A/NKG2-B type II integral membrane protein
233 a.a.
120 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   21 terms 
  Biological process     immune system process   35 terms 
  Biochemical function     protein binding     3 terms  


J Exp Med 205:725-735 (2008)
PubMed id: 18332182  
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
E.J.Petrie, C.S.Clements, J.Lin, L.C.Sullivan, D.Johnson, T.Huyton, A.Heroux, H.L.Hoare, T.Beddoe, H.H.Reid, M.C.Wilce, A.G.Brooks, J.Rossjohn.
The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A-HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a "lock and key" interaction is typical of innate receptor-ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
23334245 P.Parham, and A.Moffett (2013).
Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution.
  Nat Rev Immunol, 13, 133-144.  
20970974 A.R.Hofstetter, L.C.Sullivan, A.E.Lukacher, and A.G.Brooks (2011).
Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity.
  Curr Opin Immunol, 23, 104-110.  
22020283 J.P.Vivian, R.C.Duncan, R.Berry, G.M.O'Connor, H.H.Reid, T.Beddoe, S.Gras, P.M.Saunders, M.A.Olshina, J.M.Widjaja, C.M.Harpur, J.Lin, S.M.Maloveste, D.A.Price, B.A.Lafont, D.W.McVicar, C.S.Clements, A.G.Brooks, and J.Rossjohn (2011).
Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B.
  Nature, 479, 401-405.
PDB code: 3vh8
20882286 M.Pyzik, E.M.Gendron-Pontbriand, N.Fodil-Cornu, and S.M.Vidal (2011).
Self or nonself? That is the question: sensing of cytomegalovirus infection by innate immune receptors.
  Mamm Genome, 22, 6.  
21135867 T.Beddoe, A.G.Brooks, and J.Rossjohn (2011).
How opposites attract.
  Immunol Cell Biol, 89, 163-164.  
21467632 X.Xin, K.Higai, Y.Imaizumi, C.Suzuki, K.Ito, A.Itoh, S.Matsumoto, Y.Azuma, and K.Matsumoto (2011).
Natural killer group 2A (NKG2A) and natural killer group 2C (NKG2C) bind to sulfated glycans and α2,3-NeuAc-containing glycoproteins.
  Biol Pharm Bull, 34, 480-485.  
20038604 C.C.Oliveira, P.A.van Veelen, B.Querido, Ru, M.Sluijter, S.Laban, S.H.van der Burg, R.Offringa, and T.van Hall (2010).
The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects.
  J Exp Med, 207, 207.  
21151939 M.T.Orr, J.Wu, M.Fang, L.J.Sigal, P.Spee, T.Egebjerg, E.Dissen, S.Fossum, J.H.Phillips, and L.L.Lanier (2010).
Development and function of CD94-deficient natural killer cells.
  PLoS One, 5, e15184.  
20122941 N.G.Walpole, L.Kjer-Nielsen, L.Kostenko, J.McCluskey, A.G.Brooks, J.Rossjohn, and C.S.Clements (2010).
The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
  J Mol Biol, 397, 467-480.
PDB codes: 3kyn 3kyo
20162447 P.L.Shaw, A.N.Kirschner, T.S.Jardetzky, and R.Longnecker (2010).
Characteristics of Epstein-Barr virus envelope protein gp42.
  Virus Genes, 40, 307-319.  
  21487512 R.Biassoni, E.Ugolotti, and A.De Maria (2010).
Comparative analysis of NK-cell receptor expression and function across primate species: Perspective on antiviral defenses.
  Self Nonself, 1, 103-113.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
19834558 A.Averdam, B.Petersen, C.Rosner, J.Neff, C.Roos, M.Eberle, F.Aujard, C.Münch, W.Schempp, M.Carrington, T.Shiina, H.Inoko, F.Knaust, P.Coggill, H.Sehra, S.Beck, L.Abi-Rached, R.Reinhardt, and L.Walter (2009).
A novel system of polymorphic and diverse NK cell receptors in primates.
  PLoS Genet, 5, e1000688.  
19278418 K.Cheent, and S.I.Khakoo (2009).
Natural killer cells: integrating diversity with function.
  Immunology, 126, 449-457.  
19696636 M.Danzer, H.Polin, J.Pröll, R.Haunschmid, K.Hofer, S.Stabentheiner, C.Hackl, H.Kasparu, J.König, H.Hauser, M.Binder, R.Weiss, C.Gabriel, and O.Krieger (2009).
Clinical significance of HLA-E*0103 homozygosity on survival after allogeneic hematopoietic stem-cell transplantation.
  Transplantation, 88, 528-532.  
19472182 Y.Chen, Y.Shi, H.Cheng, Y.Q.An, and G.F.Gao (2009).
Structural immunology and crystallography help immunologists see the immune system in action: how T and NK cells touch their ligands.
  IUBMB Life, 61, 579-590.  
19604491 Y.Li, M.Hofmann, Q.Wang, L.Teng, L.K.Chlewicki, H.Pircher, and R.A.Mariuzza (2009).
Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.
  Immunity, 31, 35-46.
PDB codes: 3ff7 3ff8 3ff9
18946929 L.C.Sullivan, C.S.Clements, J.Rossjohn, and A.G.Brooks (2008).
The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity.
  Tissue Antigens, 72, 415-424.  
19036608 P.Parham (2008).
The genetic and evolutionary balances in human NK cell receptor diversity.
  Semin Immunol, 20, 311-316.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.