spacer
spacer

PDBsum entry 1kcg

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Immune system PDB id
1kcg
Jmol
Contents
Protein chains
122 a.a. *
170 a.a. *
Ligands
GSH
Waters ×122
* Residue conservation analysis
PDB id:
1kcg
Name: Immune system
Title: Nkg2d in complex with ulbp3
Structure: Nkg2-d type ii integral membrane protein. Chain: a, b. Synonym: activating nk receptor nkg2d. Engineered: yes. Ulbp3 protein. Chain: c. Synonym: class i mhc-like molecule ulbp3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Trimer (from PQS)
Resolution:
2.60Å     R-factor:   0.220     R-free:   0.268
Authors: S.Radaev,P.Sun
Key ref:
S.Radaev et al. (2001). Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3. Immunity, 15, 1039-1049. PubMed id: 11754823 DOI: 10.1016/S1074-7613(01)00241-2
Date:
08-Nov-01     Release date:   09-Jan-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P26718  (NKG2D_HUMAN) -  NKG2-D type II integral membrane protein
Seq:
Struc:
216 a.a.
122 a.a.
Protein chain
Pfam   ArchSchema ?
Q9BZM4  (N2DL3_HUMAN) -  NKG2D ligand 3
Seq:
Struc:
244 a.a.
170 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     immune response   2 terms 
  Biochemical function     carbohydrate binding     1 term  

 

 
DOI no: 10.1016/S1074-7613(01)00241-2 Immunity 15:1039-1049 (2001)
PubMed id: 11754823  
 
 
Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3.
S.Radaev, B.Rostro, A.G.Brooks, M.Colonna, P.D.Sun.
 
  ABSTRACT  
 
NKG2D is known to trigger the natural killer (NK) cell lysis of various tumor and virally infected cells. In the NKG2D/ULBP3 complex, the structure of ULBP3 resembles the alpha1 and alpha2 domains of classical MHC molecules without a bound peptide. The lack of alpha3 and beta2m domains is compensated by replacing two hydrophobic patches at the underside of the class I MHC-like beta sheet floor with a group of hydrophilic and charged residues in ULBP3. NKG2D binds diagonally across the ULBP3 alpha helices, creating a complementary interface, an asymmetrical subunit orientation, and local conformational adjustments in the receptor. The interface is stabilized primarily by hydrogen bonds and hydrophobic interactions. Unlike the KIR receptors that recognize a conserved HLA region by a lock-and-key mechanism, NKG2D recognizes diverse ligands by an induced-fit mechanism.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Structural Comparison of ULBP3 with Other Class I MHC-Related Molecules(A) Structural overlay between the NKG2D/ULBP3 (red) and NKG2D/MICA (cyan) complexes. The complexes are superimposed at the respective NKG2D. The α3 domain of MICA is omitted for clarity. The coordinates for the NKG2D/MICA complex are taken from the Protein Data Bank entry 1hyr.(B) Hydrophobic residues that fill the inside of the groove between the helices.(C) Surface representation of the interface between the α1/α2 (cyan worm) domains and the α3 and β2m domains of MHC class I. Positively charged, negatively charged, polar, and hydrophobic residues are colored blue, red, yellow, and white, respectively. Areas of α1/α2 domains contacting α3 and β2m are outlined in white and magenta, respectively. For comparison, the corresponding residues of ULBP3 (green worm) are also shown with the same color scheme. This figure and Figure 5C were generated using the program GRASP (Nicholls et al., 1991).(D) Structural comparison of the α1 and α2 domains of class I MHC with its homologs. The top panel shows the spacing of the helices in the α1 and α2 domains. The bottom panel shows the space-filling model of the putative peptide binding groove (indicated by the arrows). The groove is partially closed in the structures of FcRn, HFE, and MICA and completely disappears in ULBP3. The Protein Data Bank entries are 1efx, 1exu, 1de4, and 1b3j for HLA-Cw3, FcRn, HFE, and MICA, respectively.
Figure 5.
Figure 5. Interface Residues between NKG2D and ULBP3(A) Residues involved in hydrogen bonds (black dotted lines) and salt bridges (red dotted lines). NKG2D is colored in yellow and green for A and B subunits, respectively. ULBP3 is colored in red. Residues are colored according to their chain color. The view is similar to the front view of Figure 1A.(B) Residues involved in hydrophobic interface patches. The color scheme is the same as in (A). Tyr 152, Ile 182, Met 184, and Tyr 199 from NKG2D subunit A form a hydrophobic patch with Met 164 and Arg 168 from the α3 helix of ULBP3. The same residues from subunit B form a hydrophobic patch with Gln 79, Arg 82, Leu 83, and Ala 86 from the α1 helix of ULBP3.(C) Surface representation of the NKG2D/ULBP3 interface colored according to electrostatic potential distribution, with positive charges in blue and negative charges in red. Patches of ULBP3 in contact with A and B subunits of NKG2D are outlined in yellow and green, respectively.(D) Conformational plasticity involved in the recognition of ULBP and MICA by NKG2D. Side chains in the NKG2D/ULBP3 complex and the NKG2D/MICA complex are shown in red and cyan, respectively. Only those hydrogen bonds and salt bridges that are different between the two complexes are presented as red and cyan dotted lines for NKG2D/ULBP3 and NKG2D/MICA, respectively. In both the NKG2D/ULBP3 and the NKG2D/MICA structures, Tyr 199 of NKG2D subunit A forms a hydrogen bond with Asp 169 (Asp 163 in MICA). However, in the complex with ULBP3, Asp 169 (ULBP3) also forms a salt bridge with Lys 197 of the NKG2D subunit, whereas the same Lys 197 from the MICA-bound receptor makes a salt bridge with Asp 65 (MICA). In the ULBP3 complex, Ser 195 of NKG2D subunit A forms a hydrogen bond with Glu 72, whereas the same residue in the MICA complex is bound to Arg 64. In the MICA complex, Lys 150 of NKG2D subunit A forms a hydrogen bond with the carbonyl oxygen of Ala 150, whereas in the ULBP3 complex, the same lysine makes no hydrogen bonds and is in close contact with Arg 80 of ULBP3. In both the ULBP3 and MICA complexes, Tyr 152 of NKG2D subunit B makes hydrogen bonds with Arg 82 (Arg 74 in MICA). However, in the MICA complex, Arg 74 forms a salt bridge with Glu 201 of NKG2D, whereas in the ULBP3 complex, Glu 201 is located 4.5 Å apart from Arg 82.
 
  The above figures are reprinted by permission from Cell Press: Immunity (2001, 15, 1039-1049) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21069396 C.Hurtado, M.J.Bustos, A.G.Granja, P.de León, P.Sabina, E.López-Viñas, P.Gómez-Puertas, Y.Revilla, and A.L.Carrascosa (2011).
The African swine fever virus lectin EP153R modulates the surface membrane expression of MHC class I antigens.
  Arch Virol, 156, 219-234.  
21422170 Y.Li, Q.Wang, and R.A.Mariuzza (2011).
Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6.
  J Exp Med, 208, 703-714.  
20653426 H.Huang, X.Zheng, Z.Tian, and R.Sun (2010).
Peptide mimicry of AICL inhibits cytolysis of NK cells by blocking NKp80-AICL recognition.
  Immunol Invest, 39, 587-597.  
20032175 H.P.Su, K.Singh, A.G.Gittis, and D.N.Garboczi (2010).
The structure of the poxvirus A33 protein reveals a dimer of unique C-type lectin-like domains.
  J Virol, 84, 2502-2510.
PDB code: 3k7b
20382988 M.G.Joyce, S.Radaev, and P.D.Sun (2010).
A rational approach to heavy-atom derivative screening.
  Acta Crystallogr D Biol Crystallogr, 66, 358-365.  
20090832 S.Müller, G.Zocher, A.Steinle, and T.Stehle (2010).
Structure of the HCMV UL16-MICB complex elucidates select binding of a viral immunoevasin to diverse NKG2D ligands.
  PLoS Pathog, 6, e1000723.
PDB code: 2wy3
  20061825 J.Steigerwald, T.Raum, S.Pflanz, R.Cierpka, S.Mangold, D.Rau, P.Hoffmann, M.Kvesic, C.Zube, S.Linnerbauer, J.Lumsden, M.Sriskandarajah, P.Kufer, P.A.Baeuerle, and J.Volkland (2009).
Human IgG1 antibodies antagonizing activating receptor NKG2D on natural killer cells.
  MAbs, 1, 115-127.  
19424970 M.Wittenbrink, J.Spreu, and A.Steinle (2009).
Differential NKG2D binding to highly related human NKG2D ligands ULBP2 and RAET1G is determined by a single amino acid in the alpha2 domain.
  Eur J Immunol, 39, 1642-1651.  
19689730 N.Stern-Ginossar, and O.Mandelboim (2009).
An integrated view of the regulation of NKG2D ligands.
  Immunology, 128, 1-6.  
18447887 B.G.Lilienfeld, A.Schildknecht, L.L.Imbach, N.J.Mueller, M.K.Schneider, and J.D.Seebach (2008).
Characterization of porcine UL16-binding protein 1 endothelial cell surface expression.
  Xenotransplantation, 15, 136-144.  
18597489 E.Hooley, E.Papagrigoriou, A.Navdaev, A.V.Pandey, J.M.Clemetson, K.J.Clemetson, and J.Emsley (2008).
The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.
  Biochemistry, 47, 7831-7837.
PDB code: 3bx4
18332182 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, and J.Rossjohn (2008).
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
  J Exp Med, 205, 725-735.
PDB code: 3cdg
18022638 M.A.Zhuravleva, K.Trandem, and P.D.Sun (2008).
Structural implications of Siglec-5-mediated sialoglycan recognition.
  J Mol Biol, 375, 437-447.
PDB codes: 2zg1 2zg2 2zg3
18193361 S.J.Burgess, K.Maasho, M.Masilamani, S.Narayanan, F.Borrego, and J.E.Coligan (2008).
The NKG2D receptor: immunobiology and clinical implications.
  Immunol Res, 40, 18-34.  
18544572 W.Cao, X.Xi, Z.Wang, L.Dong, Z.Hao, L.Cui, C.Ma, and W.He (2008).
Four novel ULBP splice variants are ligands for human NKG2D.
  Int Immunol, 20, 981-991.  
17132623 A.A.Watson, J.Brown, K.Harlos, J.A.Eble, T.S.Walter, and C.A.O'Callaghan (2007).
The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2.
  J Biol Chem, 282, 3165-3172.
PDB code: 2c6u
17207160 A.Kalayciyan, and C.Zouboulis (2007).
An update on Behçet's disease.
  J Eur Acad Dermatol Venereol, 21, 1.  
16953885 J.H.Larson, B.M.Marron, J.E.Beever, B.A.Roe, and H.A.Lewin (2006).
Genomic organization and evolution of the ULBP genes in cattle.
  BMC Genomics, 7, 227.  
16737824 L.Deng, and R.A.Mariuzza (2006).
Structural basis for recognition of MHC and MHC-like ligands by natural killer cell receptors.
  Semin Immunol, 18, 159-166.  
16699187 S.Radaev, S.Li, and P.D.Sun (2006).
A survey of protein-protein complex crystallizations.
  Acta Crystallogr D Biol Crystallogr, 62, 605-612.  
15939022 I.Ohki, T.Ishigaki, T.Oyama, S.Matsunaga, Q.Xie, M.Ohnishi-Kameyama, T.Murata, D.Tsuchiya, S.Machida, K.Morikawa, and S.Tate (2005).
Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL.
  Structure, 13, 905-917.
PDB codes: 1yxj 1yxk
15771571 L.L.Lanier (2005).
NK cell recognition.
  Annu Rev Immunol, 23, 225-274.  
20476991 R.Biassoni, and N.Dimasi (2005).
Human natural killer cell receptor functions and their implication in diseases.
  Expert Rev Clin Immunol, 1, 405-417.  
12802013 A.Sato, W.E.Mayer, P.Overath, and J.Klein (2003).
Genes encoding putative natural killer cell C-type lectin receptors in teleostean fishes.
  Proc Natl Acad Sci U S A, 100, 7779-7784.  
14670298 B.J.McFarland, and R.K.Strong (2003).
Thermodynamic analysis of degenerate recognition by the NKG2D immunoreceptor: not induced fit but rigid adaptation.
  Immunity, 19, 803-812.  
14670294 D.H.Margulies (2003).
Molecular interactions: stiff or floppy (or somewhere in between?).
  Immunity, 19, 772-774.  
14523385 D.H.Raulet (2003).
Roles of the NKG2D immunoreceptor and its ligands.
  Nat Rev Immunol, 3, 781-790.  
12782717 I.H.Westgaard, E.Dissen, K.M.Torgersen, S.Lazetic, L.L.Lanier, J.H.Phillips, and S.Fossum (2003).
The lectin-like receptor KLRE1 inhibits natural killer cell cytotoxicity.
  J Exp Med, 197, 1551-1561.  
12913002 J.F.Head, T.R.Mealy, F.X.McCormack, and B.A.Seaton (2003).
Crystal structure of trimeric carbohydrate recognition and neck domains of surfactant protein A.
  J Biol Chem, 278, 43254-43260.
PDB codes: 1r13 1r14
14563312 M.Gleimer, and P.Parham (2003).
Stress management: MHC class I and class I-like molecules as reporters of cellular stress.
  Immunity, 19, 469-477.  
12471063 S.Radaev, and P.D.Sun (2003).
Structure and function of natural killer cell surface receptors.
  Annu Rev Biophys Biomol Struct, 32, 93.  
12669021 W.M.Yokoyama, and B.F.Plougastel (2003).
Immune functions encoded by the natural killer gene complex.
  Nat Rev Immunol, 3, 304-316.  
12668644 X.Saulquin, L.N.Gastinel, and E.Vivier (2003).
Crystal structure of the human natural killer cell activating receptor KIR2DS2 (CD158j).
  J Exp Med, 197, 933-938.
PDB code: 1m4k
12115588 C.Menier, B.Riteau, E.D.Carosella, and N.Rouas-Freiss (2002).
MICA triggering signal for NK cell tumor lysis is counteracted by HLA-G1-mediated inhibitory signal.
  Int J Cancer, 100, 63-70.  
11973127 E.Vivier, E.Tomasello, and P.Paul (2002).
Lymphocyte activation via NKG2D: towards a new paradigm in immune recognition?
  Curr Opin Immunol, 14, 306-311.  
12183162 K.L.McQueen, and P.Parham (2002).
Variable receptors controlling activation and inhibition of NK cells.
  Curr Opin Immunol, 14, 615-621.  
12077428 P.D.Sun, and S.Radaev (2002).
Generating isomorphous heavy-atom derivatives by a quick-soak method. Part II: phasing of new structures.
  Acta Crystallogr D Biol Crystallogr, 58, 1099-1103.  
12052146 S.Balasubramanian, P.Harrison, H.Hegyi, P.Bertone, N.Luscombe, N.Echols, P.McGarvey, Z.Zhang, and M.Gerstein (2002).
SNPs on human chromosomes 21 and 22 -- analysis in terms of protein features and pseudogenes.
  Pharmacogenomics, 3, 393-402.  
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.