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Immunoreceptor PDB id
1ah1
Jmol
Contents
Protein chain
129 a.a. *
Ligands
NAG-NAG-FUL-BMA
NAG-NAG-FUC-BMA
* Residue conservation analysis
PDB id:
1ah1
Name: Immunoreceptor
Title: Ctla-4, nmr, 20 structures
Structure: Ctla-4. Chain: a. Fragment: extracellular n-terminal immunoglobulin v-like. Synonym: cd152. Engineered: yes. Other_details: tetrasaccharide core (glcnac, glcnac, fucose attached at n 78 and n 111
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho
NMR struc: 20 models
Authors: W.J.Metzler,J.Bajorath,W.Fenderson,S.-Y.Shaw,R.Peach,K.L.Con J.Naemura,G.Leytze,T.B.Lavoie,L.Mueller,P.S.Linsley
Key ref: W.J.Metzler et al. (1997). Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28. Nat Struct Biol, 4, 527-531. PubMed id: 9228944 DOI: 10.1038/nsb0797-527
Date:
11-Apr-97     Release date:   15-Apr-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P16410  (CTLA4_HUMAN) -  Cytotoxic T-lymphocyte protein 4
Seq:
Struc:
223 a.a.
129 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     immune response   1 term 

 

 
DOI no: 10.1038/nsb0797-527 Nat Struct Biol 4:527-531 (1997)
PubMed id: 9228944  
 
 
Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28.
W.J.Metzler, J.Bajorath, W.Fenderson, S.Y.Shaw, K.L.Constantine, J.Naemura, G.Leytze, R.J.Peach, T.B.Lavoie, L.Mueller, P.S.Linsley.
 
  ABSTRACT  
 
The structure of human CTLA-4 reveals that residues Met 99, Tyr 100 and Tyr 104 of the M99YPPPY104 motif are adjacent to a patch of charged surface residues on the A'GFCC' face of the protein. Mutation of these residues, which are conserved in the CTLA-4/CD28 family, significantly reduces binding to CD80 and/or CD86, implicating this patch as a ligand binding site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21349284 S.Zhu, S.Liu, L.Wan, G.Yang, H.Yang, J.Cheng, and X.Lu (2011).
Molecular cloning, expression and characterization of the functional domain of CTLA4 from the rhesus monkey, Macaca mulatta.
  Dev Comp Immunol, 35, 736-744.  
20801597 Z.Chen, R.Liu, J.Che, H.Shi, Y.Hou, Y.Liu, L.Sun, L.Tan, C.Shan, P.Hu, and Y.Cheng (2011).
Qualitative and quantitative studies on human B7.1-Fc fusion protein and the application in pharmacokinetic study in rhesus monkeys.
  J Pharm Biomed Anal, 54, 133-140.  
19690964 L.Skrisovska, M.Schubert, and F.H.Allain (2010).
Recent advances in segmental isotope labeling of proteins: NMR applications to large proteins and glycoproteins.
  J Biomol NMR, 46, 51-65.  
19426215 T.Pentcheva-Hoang, E.Corse, and J.P.Allison (2009).
Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections.
  Immunol Rev, 229, 67-87.  
17497145 G.P.Bondinas, A.K.Moustakas, and G.K.Papadopoulos (2007).
The spectrum of HLA-DQ and HLA-DR alleles, 2006: a listing correlating sequence and structure with function.
  Immunogenetics, 59, 539-553.  
17072314 G.Szakonyi, M.G.Klein, J.P.Hannan, K.A.Young, R.Z.Ma, R.Asokan, V.M.Holers, and X.S.Chen (2006).
Structure of the Epstein-Barr virus major envelope glycoprotein.
  Nat Struct Mol Biol, 13, 996.
PDB code: 2h6o
16551244 W.A.Teft, M.G.Kirchhof, and J.Madrenas (2006).
A molecular perspective of CTLA-4 function.
  Annu Rev Immunol, 24, 65-97.  
16169851 D.M.Compaan, L.C.Gonzalez, I.Tom, K.M.Loyet, D.Eaton, and S.G.Hymowitz (2005).
Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex.
  J Biol Chem, 280, 39553-39561.
PDB code: 2aw2
15696168 E.J.Evans, R.M.Esnouf, R.Manso-Sancho, R.J.Gilbert, J.R.James, C.Yu, J.A.Fennelly, C.Vowles, T.Hanke, B.Walse, T.Hünig, P.Sørensen, D.I.Stuart, and S.J.Davis (2005).
Crystal structure of a soluble CD28-Fab complex.
  Nat Immunol, 6, 271-279.
PDB code: 1yjd
15598660 M.Srinivasan, D.Lu, R.Eri, D.D.Brand, A.Haque, and J.S.Blum (2005).
CD80 binding polyproline helical peptide inhibits T cell activation.
  J Biol Chem, 280, 10149-10155.  
15163715 J.F.Giguère, S.Bounou, J.S.Paquette, J.Madrenas, and M.J.Tremblay (2004).
Insertion of host-derived costimulatory molecules CD80 (B7.1) and CD86 (B7.2) into human immunodeficiency virus type 1 affects the virus life cycle.
  J Virol, 78, 6222-6232.  
15030777 X.Zhang, J.C.Schwartz, X.Guo, S.Bhatia, E.Cao, M.Lorenz, M.Cammer, L.Chen, Z.Y.Zhang, M.A.Edidin, S.G.Nathenson, and S.C.Almo (2004).
Structural and functional analysis of the costimulatory receptor programmed death-1.
  Immunity, 20, 337-347.
PDB code: 1npu
12707298 D.H.Margulies (2003).
CD28, costimulator or agonist receptor?
  J Exp Med, 197, 949-953.  
12707299 F.Lühder, Y.Huang, K.M.Dennehy, C.Guntermann, I.Müller, E.Winkler, T.Kerkau, S.Ikemizu, S.J.Davis, T.Hanke, and T.Hünig (2003).
Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists.
  J Exp Med, 197, 955-966.  
12615890 P.A.van der Merwe, and S.J.Davis (2003).
Molecular interactions mediating T cell antigen recognition.
  Annu Rev Immunol, 21, 659-684.  
12719480 S.Wang, J.Bajorath, D.B.Flies, H.Dong, T.Honjo, and L.Chen (2003).
Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction.
  J Exp Med, 197, 1083-1091.  
12244107 S.Anjos, A.Nguyen, H.Ounissi-Benkalha, M.C.Tessier, and C.Polychronakos (2002).
A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele.
  J Biol Chem, 277, 46478-46486.  
12167647 S.Lazetic, S.R.Leong, J.C.Chang, R.Ong, G.Dawes, and J.Punnonen (2002).
Chimeric co-stimulatory molecules that selectively act through CD28 or CTLA-4 on human T cells.
  J Biol Chem, 277, 38660-38668.  
11956294 S.Wang, G.Zhu, K.Tamada, L.Chen, and J.Bajorath (2002).
Ligand binding sites of inducible costimulator and high avidity mutants with improved function.
  J Exp Med, 195, 1033-1041.  
  11274928 C.A.Chambers (2001).
The expanding world of co-stimulation: the two-signal model revisited.
  Trends Immunol, 22, 217-223.  
11052947 D.A.Ostrov, W.Shi, J.C.Schwartz, S.C.Almo, and S.G.Nathenson (2000).
Structure of murine CTLA-4 and its role in modulating T cell responsiveness.
  Science, 290, 816-819.
PDB code: 1dqt
10744968 D.L.Mueller (2000).
T cells: A proliferation of costimulatory molecules.
  Curr Biol, 10, R227-R230.  
  10975572 K.L.Bennett, M.Kussmann, P.Björk, M.Godzwon, M.Mikkelsen, P.Sørensen, and P.Roepstorff (2000).
Chemical cross-linking with thiol-cleavable reagents combined with differential mass spectrometric peptide mapping--a novel approach to assess intermolecular protein contacts.
  Protein Sci, 9, 1503-1518.  
10861932 M.A.Bowen, A.A.Aruffo, and J.Bajorath (2000).
Cell surface receptors and their ligands: in vitro analysis of CD6-CD166 interactions.
  Proteins, 40, 420-428.  
10777098 M.P.Pistillo, P.L.Tazzari, J.H.Ellis, and G.B.Ferrara (2000).
Molecular characterization and applications of recombinant scFv antibodies to CD152 co-stimulatory molecule.
  Tissue Antigens, 55, 229-238.  
10661405 S.Ikemizu, R.J.Gilbert, J.A.Fennelly, A.V.Collins, K.Harlos, E.Y.Jones, D.I.Stuart, and S.J.Davis (2000).
Structure and dimerization of a soluble form of B7-1.
  Immunity, 12, 51-60.
PDB code: 1dr9
10209159 C.A.Chambers, and J.P.Allison (1999).
Costimulatory regulation of T cell function.
  Curr Opin Cell Biol, 11, 203-210.  
10095786 P.J.Erbel, Y.Karimi-Nejad, T.De Beer, R.Boelens, J.P.Kamerling, and J.F.Vliegenthart (1999).
Solution structure of the alpha-subunit of human chorionic gonadotropin.
  Eur J Biochem, 260, 490-498.
PDB code: 1dz7
10398368 S.D.Nuttall, M.J.Rousch, R.A.Irving, S.E.Hufton, H.R.Hoogenboom, and P.J.Hudson (1999).
Design and expression of soluble CTLA-4 variable domain as a scaffold for the display of functional polypeptides.
  Proteins, 36, 217-227.  
9844829 P.Scheipers, and H.Reiser (1998).
Role of the CTLA-4 receptor in T cell activation and immunity. Physiologic function of the CTLA-4 receptor.
  Immunol Res, 18, 103-115.  
9700513 S.J.Davis, S.Ikemizu, M.K.Wild, and P.A.van der Merwe (1998).
CD2 and the nature of protein interactions mediating cell-cell recognition.
  Immunol Rev, 163, 217-236.  
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.