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Immune system PDB-id
1hyr
Asymmetric unit
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Contents
Description
Header details
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References
PROCHECK
Protein chains
128 a.a. *
275 a.a. *
Waters ×46

* Residue conservation analysis
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  Biological unit*, dodecamer
(*as deduced by PQS)
PDB id: 1hyr
Name: Immune system
Title: Crystal structure of human mica in complex with natural killer cell receptor nkg2d

Structure:
Nkg2-d type ii integral membrane protein. Chain: b, a. Fragment: extracellular domain (residues 80 to 216). Synonym: nkg2d. Engineered: yes. Mhc class i chain-related protein a. Chain: c. Fragment: extracellular domain (residues 1 to 274). Synonym: mic-a, mic, perb11.

Source:
Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cell surface. Gene: nkg2d. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: mica-001. Expressed in: escherichia coli.

Biological unit:
Dodecamer (from PQS)

UniProt:
Chains B, A: P26718 (NKG2D_HUMAN)
Pfam   ArchSchema ?
Seq: 216 a.a.
Struc: 128 a.a.

Chain C: Q29983 (MICA_HUMAN)
Pfam   ArchSchema ?
Seq:
Struc:
Seq: 383 a.a.
Struc: 275 a.a.*
Key:    PfamA domain
 Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

Resolution:
2.70Å

R-factor:
0.227

R-free:
0.282

Authors:
P.Li,R.K.Strong

Key ref:
P.Li et al. (2001). Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA.. Nat Immunol, 2, 443-451. [PubMed id: 11323699] [DOI: 10.1038/87757]

Date:
21-Jan-01

Release date:
23-May-01
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    Key reference    
 
 
DOI no: 10.1038/87757 Nat Immunol 2:443-451 (2001)
PubMed id: 11323699  
 
 
Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA.
P.Li, D.L.Morris, B.E.Willcox, A.Steinle, T.Spies, R.K.Strong.
 
  ABSTRACT  
 
The major histocompatibility complex (MHC) class I homolog, MICA, is a stress-inducible ligand for NKG2D, a C-type lectin-like activating immunoreceptor. The crystal structure of this ligand-receptor complex that we report here reveals an NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to that seen in T cell receptor-MHC class I protein complexes. Similar surfaces on each NKG2D monomer interact with different surfaces on either the alpha1 or alpha2 domains of MICA. The binding interactions are large in area and highly complementary. The central section of the alpha2-domain helix, disordered in the structure of MICA alone, is ordered in the complex and forms part of the NKG2D interface. The extensive flexibility of the interdomain linker of MICA is shown by its altered conformation when crystallized alone or in complex with NKG2D.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  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
19604395 C.L.Mayer, W.K.Snyder, M.A.Swietlicka, A.D.Vanschoiack, C.R.Austin, and B.J.McFarland (2009).
Size-exclusion chromatography can identify faster-associating protein complexes and evaluate design strategies.
  BMC Res Notes, 2, 135.  
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.  
19353249 R.Kopp, J.Glas, U.Lau-Werner, E.D.Albert, and E.H.Weiss (2009).
Association of MICA-TM and MICB C1_2_A microsatellite polymorphisms with tumor progression in patients with colorectal cancer.
  J Clin Immunol, 29, 545-554.  
18560379 B.A.Rabinovich, R.R.Ketchem, M.Wolfson, L.Goldstein, M.Skelly, and D.Cosman (2008).
A role for the MHC class I-like Mill molecules in nutrient metabolism and wound healing.
  Immunol Cell Biol, 86, 489-496.  
18448674 B.K.Kaiser, J.C.Pizarro, J.Kerns, and R.K.Strong (2008).
Structural basis for NKG2A/CD94 recognition of HLA-E.
  Proc Natl Acad Sci U S A, 105, 6696-6701.
PDB code: 3cii
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
18426793 L.Deng, S.Cho, E.L.Malchiodi, M.C.Kerzic, J.Dam, and R.A.Mariuzza (2008).
Molecular architecture of the major histocompatibility complex class I-binding site of Ly49 natural killer cell receptors.
  J Biol Chem, 283, 16840-16849.
PDB codes: 3c8j 3c8k 3cad
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.  
18574582 S.L.Rogers, and J.Kaufman (2008).
High allelic polymorphism, moderate sequence diversity and diversifying selection for B-NK but not B-lec, the pair of lectin-like receptor genes in the chicken MHC.
  Immunogenetics, 60, 461-475.  
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.  
18309314 W.Held, and R.A.Mariuzza (2008).
Cis interactions of immunoreceptors with MHC and non-MHC ligands.
  Nat Rev Immunol, 8, 269-278.  
17216437 A.Averdam, S.Seelke, I.Grützner, C.Rosner, C.Roos, N.Westphal, C.Stahl-Hennig, V.Muppala, A.Schrod, U.Sauermann, R.Dressel, and L.Walter (2007).
Genotyping and segregation analyses indicate the presence of only two functional MIC genes in rhesus macaques.
  Immunogenetics, 59, 247-251.  
17614877 A.R.Mistry, and C.A.O'Callaghan (2007).
Regulation of ligands for the activating receptor NKG2D.
  Immunology, 121, 439-447.  
17495932 B.K.Kaiser, D.Yim, I.T.Chow, S.Gonzalez, Z.Dai, H.H.Mann, R.K.Strong, V.Groh, and T.Spies (2007).
Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands.
  Nature, 447, 482-486.  
17690100 C.S.Lengyel, L.J.Willis, P.Mann, D.Baker, T.Kortemme, R.K.Strong, and B.J.McFarland (2007).
Mutations designed to destabilize the receptor-bound conformation increase MICA-NKG2D association rate and affinity.
  J Biol Chem, 282, 30658-30666.  
17911424 G.Gambelunghe, A.Brozzetti, M.Ghaderi, P.Candeloro, C.Tortoioli, and A.Falorni (2007).
MICA gene polymorphism in the pathogenesis of type 1 diabetes.
  Ann N Y Acad Sci, 1110, 92-98.  
17195078 I.Lionello, P.Mangia, L.Gattinoni, D.Pende, A.Cippone, M.Sensi, P.Rigatti, and C.Traversari (2007).
CD8(+) T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway.
  Cancer Immunol Immunother, 56, 1065-1076.  
17285285 J.Birch, and S.A.Ellis (2007).
Complexity in the cattle CD94/NKG2 gene families.
  Immunogenetics, 59, 273-280.  
16485126 R.Solana, J.G.Casado, E.Delgado, O.DelaRosa, J.Marín, E.Durán, G.Pawelec, and R.Tarazona (2007).
Lymphocyte activation in response to melanoma: interaction of NK-associated receptors and their ligands.
  Cancer Immunol Immunother, 56, 101-109.  
  16500675 K.Natarajan, A.Hicks, J.Mans, H.Robinson, R.Guan, R.A.Mariuzza, and D.H.Margulies (2006).
Crystal structure of the murine cytomegalovirus MHC-I homolog m144.
  J Mol Biol, 358, 157-171.
PDB code: 1u58
16551255 M.G.Rudolph, R.L.Stanfield, and I.A.Wilson (2006).
How TCRs bind MHCs, peptides, and coreceptors.
  Annu Rev Immunol, 24, 419-466.  
16336259 A.N.Zelensky, and J.E.Gready (2005).
The C-type lectin-like domain superfamily.
  FEBS J, 272, 6179-6217.  
15894612 D.Garrity, M.E.Call, J.Feng, and K.W.Wucherpfennig (2005).
The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure.
  Proc Natl Acad Sci U S A, 102, 7641-7646.  
15821084 E.J.Adams, Y.H.Chien, and K.C.Garcia (2005).
Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22.
  Science, 308, 227-231.
PDB code: 1ypz
15771571 L.L.Lanier (2005).
NK cell recognition.
  Annu Rev Immunol, 23, 225-274.  
15858601 L.Windsor, M.Puschendorf, R.Allcock, A.Scott, D.Sayer, R.Kucharzak, I.Gut, V.McCann, E.Davis, C.Witt, F.Christiansen, and P.Price (2005).
Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?
  Genes Immun, 6, 298-304.  
16089503 R.Olson, K.E.Huey-Tubman, C.Dulac, and P.J.Bjorkman (2005).
Structure of a pheromone receptor-associated MHC molecule with an open and empty groove.
  PLoS Biol, 3, e257.
PDB code: 1zs8
15304008 M.Schroeder, H.A.Elsner, T.D.Kim, and R.Blasczyk (2004).
Eight novel MICB alleles, including a null allele, identified in gastric MALT lymphoma patients.
  Tissue Antigens, 64, 276-280.  
15131306 X.L.He, and K.C.Garcia (2004).
Structure of nerve growth factor complexed with the shared neurotrophin receptor p75.
  Science, 304, 870-875.
PDB code: 1sg1
12653967 A.M.Wong, R.J.Allcock, K.Y.Cheong, F.T.Christiansen, and P.Price (2003).
Alleles of the proximal promoter of BAT1, a putative anti-inflammatory gene adjacent to the TNF cluster, reduce transcription on a disease-associated MHC haplotype.
  Genes Cells, 8, 403-412.  
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.  
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.  
12411439 R.K.Strong, M.A.Holmes, P.Li, L.Braun, N.Lee, and D.E.Geraghty (2003).
HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities.
  J Biol Chem, 278, 5082-5090.
PDB codes: 1kpr 1ktl
12471063 S.Radaev, and P.D.Sun (2003).
Structure and function of natural killer cell surface receptors.
  Annu Rev Biophys Biomol Struct, 32, 93.  
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.  
12445274 F.E.McCann, K.Suhling, L.M.Carlin, K.Eleme, S.B.Taner, K.Yanagi, B.Vanherberghen, P.M.French, and D.M.Davis (2002).
Imaging immune surveillance by T cells and NK cells.
  Immunol Rev, 189, 179-192.  
11861620 K.Natarajan, N.Dimasi, J.Wang, R.A.Mariuzza, and D.H.Margulies (2002).
Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination.
  Annu Rev Immunol, 20, 853-885.  
12501157 R.L.Rich, and D.G.Myszka (2002).
Survey of the year 2001 commercial optical biosensor literature.
  J Mol Recognit, 15, 352-376.  
11880613 T.Spies (2002).
Induction of T cell alertness by bacterial colonization of intestinal epithelium.
  Proc Natl Acad Sci U S A, 99, 2584-2586.  
11830641 V.Tieng, C.Le Bouguénec, L.du Merle, P.Bertheau, P.Desreumaux, A.Janin, D.Charron, and A.Toubert (2002).
Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA.
  Proc Natl Acad Sci U S A, 99, 2977-2982.  
12392510 Y.S.Park, C.B.Sanjeevi, D.Robles, L.Yu, M.Rewers, P.A.Gottlieb, P.Fain, and G.S.Eisenbarth (2002).
Additional association of intra-MHC genes, MICA and D6S273, with Addison's disease.
  Tissue Antigens, 60, 155-163.  
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.