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PDBsum entry 2akr
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Immune system PDB id
2akr

 

 

 

 

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Contents
Protein chains
269 a.a. *
98 a.a. *
Ligands
NAG-NAG
NAG ×5
CIS ×2
Waters ×748
* Residue conservation analysis
PDB id:
2akr
Name: Immune system
Title: Structural basis of sulfatide presentation by mouse cd1d
Structure: T-cell surface glycoprotein cd1d1. Chain: a, c. Fragment: extracellular domain, residues 19-297. Synonym: cd1.1 antigen. Engineered: yes. Beta-2-microglobulin. Chain: b, d. Fragment: residues 21-119. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: cd1d1, cd1.1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: b2m.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.187     R-free:   0.249
Authors: D.M.Zajonc,R.Halder,D.Wu,I.Maricic,K.Roy,C.-H.Wong,V.Kumar,I.A.Wilson
Key ref: D.M.Zajonc et al. (2005). Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med, 202, 1517-1526. PubMed id: 16314439
Date:
03-Aug-05     Release date:   06-Dec-05    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11609  (CD1D1_MOUSE) -  Antigen-presenting glycoprotein CD1d1 from Mus musculus
Seq:
Struc: 		336 a.a.
269 a.a.
Protein chains
Pfam   ArchSchema ?
P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus
Seq:
Struc: 		119 a.a.
98 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
J Exp Med 202:1517-1526 (2005)
PubMed id: 16314439  
 
 
Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity.
D.M.Zajonc, I.Maricic, D.Wu, R.Halder, K.Roy, C.H.Wong, V.Kumar, I.A.Wilson.
 
  ABSTRACT  
 
Sulfatide derived from the myelin stimulates a distinct population of CD1d-restricted natural killer T (NKT) cells. Cis-tetracosenoyl sulfatide is one of the immunodominant species in myelin as identified by proliferation, cytokine secretion, and CD1d tetramer staining. The crystal structure of mouse CD1d in complex with cis-tetracosenoyl sulfatide at 1.9 A resolution reveals that the longer cis-tetracosenoyl fatty acid chain fully occupies the A' pocket of the CD1d binding groove, whereas the sphingosine chain fills up the F' pocket. A precise hydrogen bond network in the center of the binding groove orients and positions the ceramide backbone for insertion of the lipid tails in their respective pockets. The 3'-sulfated galactose headgroup is highly exposed for presentation to the T cell receptor and projects up and away from the binding pocket due to its beta linkage, compared with the more intimate binding of the alpha-glactosyl ceramide headgroup to CD1d. These structure and binding data on sulfatide presentation by CD1d have important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21393632 M.Hashimoto, K.Hiwatashi, K.Ichiyama, R.Morita, T.Sekiya, A.Kimura, Y.Sugiyama, T.Sibata, K.Kuroda, R.Takahashi, and A.Yoshimura (2011).
SOCS1 regulates type I/type II NKT cell balance by regulating IFN{gamma} signaling.
  Int Immunol, 23, 165-176.  
21087900 M.J.van den Heuvel, N.Garg, L.Van Kaer, and S.M.Haeryfar (2011).
NKT cell costimulation: experimental progress and therapeutic promise.
  Trends Mol Med, 17, 65-77.  
21552205 S.Aspeslagh, Y.Li, E.D.Yu, N.Pauwels, M.Trappeniers, E.Girardi, T.Decruy, K.Van Beneden, K.Venken, M.Drennan, L.Leybaert, J.Wang, R.W.Franck, S.Van Calenbergh, D.M.Zajonc, and D.Elewaut (2011).
Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.
  EMBO J, 30, 2294-2305.
PDB codes: 3qux 3quy 3quz
21376640 T.Mallevaey, A.J.Clarke, J.P.Scott-Browne, M.H.Young, L.C.Roisman, D.G.Pellicci, O.Patel, J.P.Vivian, J.L.Matsuda, J.McCluskey, D.I.Godfrey, P.Marrack, J.Rossjohn, and L.Gapin (2011).
A molecular basis for NKT cell recognition of CD1d-self-antigen.
  Immunity, 34, 315-326.
PDB codes: 3au1 3qi9
19949076 B.A.Sullivan, N.A.Nagarajan, G.Wingender, J.Wang, I.Scott, M.Tsuji, R.W.Franck, S.A.Porcelli, D.M.Zajonc, and M.Kronenberg (2010).
Mechanisms for glycolipid antigen-driven cytokine polarization by Valpha14i NKT cells.
  J Immunol, 184, 141-153.
PDB code: 3g08
  20953368 B.Leung, and H.W.Harris (2010).
NKT cells in sepsis.
  Clin Dev Immunol, 2010, 0.  
21179412 G.Bricard, M.M.Venkataswamy, K.O.Yu, J.S.Im, R.M.Ndonye, A.R.Howell, N.Veerapen, P.A.Illarionov, G.S.Besra, Q.Li, Y.T.Chang, and S.A.Porcelli (2010).
Α-galactosylceramide analogs with weak agonist activity for human iNKT cells define new candidate anti-inflammatory agents.
  PLoS One, 5, e14374.  
20080535 J.Wang, Y.Li, Y.Kinjo, T.T.Mac, D.Gibson, G.F.Painter, M.Kronenberg, and D.M.Zajonc (2010).
Lipid binding orientation within CD1d affects recognition of Borrelia burgorferi antigens by NKT cells.
  Proc Natl Acad Sci U S A, 107, 1535-1540.
PDB codes: 3ilp 3ilq
21167756 L.Scharf, N.S.Li, A.J.Hawk, D.Garzón, T.Zhang, L.M.Fox, A.R.Kazen, S.Shah, E.J.Haddadian, J.E.Gumperz, A.Saghatelian, J.D.Faraldo-Gómez, S.C.Meredith, J.A.Piccirilli, and E.J.Adams (2010).
The 2.5 å structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation.
  Immunity, 33, 853-862.
PDB code: 3ov6
19945296 M.M.Venkataswamy, and S.A.Porcelli (2010).
Lipid and glycolipid antigens of CD1d-restricted natural killer T cells.
  Semin Immunol, 22, 68-78.  
20534460 P.Arrenberg, R.Halder, Y.Dai, I.Maricic, and V.Kumar (2010).
Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a beta-linked self-glycolipid.
  Proc Natl Acad Sci U S A, 107, 10984-10989.  
20921281 Y.Li, E.Girardi, J.Wang, E.D.Yu, G.F.Painter, M.Kronenberg, and D.M.Zajonc (2010).
The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode.
  J Exp Med, 207, 2383-2393.
PDB codes: 3o8x 3o9w
19732779 A.Schiefner, M.Fujio, D.Wu, C.H.Wong, and I.A.Wilson (2009).
Structural evaluation of potent NKT cell agonists: implications for design of novel stimulatory ligands.
  J Mol Biol, 394, 71-82.
PDB codes: 3gml 3gmm 3gmn 3gmo 3gmp 3gmq 3gmr
19415116 D.Cox, L.Fox, R.Tian, W.Bardet, M.Skaley, D.Mojsilovic, J.Gumperz, and W.Hildebrand (2009).
Determination of cellular lipids bound to human CD1d molecules.
  PLoS ONE, 4, e5325.  
19594637 D.M.Zajonc, and M.Kronenberg (2009).
Carbohydrate specificity of the recognition of diverse glycolipids by natural killer T cells.
  Immunol Rev, 230, 188-200.  
  19246642 G.Lalazar, A.Ben Ya'acov, D.M.Livovsky, M.El Haj, O.Pappo, S.Preston, L.Zolotarov, and Y.Ilan (2009).
Beta-glycoglycosphingolipid-induced alterations of the STAT signaling pathways are dependent on CD1d and the lipid raft protein flotillin-2.
  Am J Pathol, 174, 1390-1399.  
19468063 I.Van Rhijn, D.C.Young, A.De Jong, J.Vazquez, T.Y.Cheng, R.Talekar, D.Barral, L.León, M.B.Brenner, J.T.Katz, R.Riese, R.M.Ruprecht, P.B.O'Connor, C.E.Costello, S.A.Porcelli, V.Briken, and D.B.Moody (2009).
CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids.
  J Exp Med, 206, 1409-1422.  
19689293 J.A.Berzofsky, and M.Terabe (2009).
The contrasting roles of NKT cells in tumor immunity.
  Curr Mol Med, 9, 667-672.  
19582739 M.Blomqvist, S.Rhost, S.Teneberg, L.Löfbom, T.Osterbye, M.Brigl, J.E.Månsson, and S.L.Cardell (2009).
Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells.
  Eur J Immunol, 39, 1726-1735.  
19627191 M.L.Lang (2009).
How do natural killer T cells help B cells?
  Expert Rev Vaccines, 8, 1109-1121.  
19342656 W.Yuan, S.J.Kang, J.E.Evans, and P.Cresswell (2009).
Natural lipid ligands associated with human CD1d targeted to different subcellular compartments.
  J Immunol, 182, 4784-4791.  
18342005 D.I.Godfrey, J.Rossjohn, and J.McCluskey (2008).
The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
  Immunity, 28, 304-314.  
19004781 D.M.Zajonc, H.Striegl, C.C.Dascher, and I.A.Wilson (2008).
The crystal structure of avian CD1 reveals a smaller, more primordial antigen-binding pocket compared to mammalian CD1.
  Proc Natl Acad Sci U S A, 105, 17925-17930.
PDB code: 3dbx
18295796 D.M.Zajonc, P.B.Savage, A.Bendelac, I.A.Wilson, and L.Teyton (2008).
Crystal structures of mouse CD1d-iGb3 complex and its cognate Valpha14 T cell receptor suggest a model for dual recognition of foreign and self glycolipids.
  J Mol Biol, 377, 1104-1116.
PDB codes: 2q7y 2q86
18006319 D.Wu, M.Fujio, and C.H.Wong (2008).
Glycolipids as immunostimulating agents.
  Bioorg Med Chem, 16, 1073-1083.  
18253930 G.Denkberg, V.S.Stronge, E.Zahavi, P.Pittoni, R.Oren, D.Shepherd, M.Salio, C.McCarthy, P.A.Illarionov, A.van der Merwe, G.S.Besra, P.Dellabona, G.Casorati, V.Cerundolo, and Y.Reiter (2008).
Phage display-derived recombinant antibodies with TCR-like specificity against alpha-galactosylceramide and its analogues in complex with human CD1d molecules.
  Eur J Immunol, 38, 829-840.  
18758473 G.Haskó, J.Linden, B.Cronstein, and P.Pacher (2008).
Adenosine receptors: therapeutic aspects for inflammatory and immune diseases.
  Nat Rev Drug Discov, 7, 759-770.  
18593354 J.D.Silk, M.Salio, J.Brown, E.Y.Jones, and V.Cerundolo (2008).
Structural and functional aspects of lipid binding by CD1 molecules.
  Annu Rev Cell Dev Biol, 24, 369-395.  
18716938 J.E.Boyson, I.Aktan, D.A.Barkhuff, and A.Chant (2008).
NKT cells at the maternal-fetal interface.
  Immunol Invest, 37, 565-582.  
18538591 M.Relloso, T.Y.Cheng, J.S.Im, E.Parisini, C.Roura-Mir, C.DeBono, D.M.Zajonc, L.F.Murga, M.J.Ondrechen, I.A.Wilson, S.A.Porcelli, and D.B.Moody (2008).
pH-dependent interdomain tethers of CD1b regulate its antigen capture.
  Immunity, 28, 774-786.  
19055947 M.Terabe, and J.A.Berzofsky (2008).
The role of NKT cells in tumor immunity.
  Adv Cancer Res, 101, 277-348.  
20476964 N.Kadri, M.Blomqvist, and S.L.Cardell (2008).
Type II natural killer T cells: a new target for immunomodulation?
  Expert Rev Clin Immunol, 4, 615-627.  
18304006 P.Marrack, J.P.Scott-Browne, S.Dai, L.Gapin, and J.W.Kappler (2008).
Evolutionarily conserved amino acids that control TCR-MHC interaction.
  Annu Rev Immunol, 26, 171-203.  
19053208 S.Kim, S.Lalani, V.V.Parekh, L.Wu, and L.Van Kaer (2008).
Glycolipid ligands of invariant natural killer T cells as vaccine adjuvants.
  Expert Rev Vaccines, 7, 1519-1532.  
17150027 A.Bendelac, P.B.Savage, and L.Teyton (2007).
The biology of NKT cells.
  Annu Rev Immunol, 25, 297-336.  
17485514 C.McCarthy, D.Shepherd, S.Fleire, V.S.Stronge, M.Koch, P.A.Illarionov, G.Bossi, M.Salio, G.Denkberg, F.Reddington, A.Tarlton, B.G.Reddy, R.R.Schmidt, Y.Reiter, G.M.Griffiths, P.A.van der Merwe, G.S.Besra, E.Y.Jones, F.D.Batista, and V.Cerundolo (2007).
The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation.
  J Exp Med, 204, 1131-1144.  
17951048 D.M.Zajonc, and M.Kronenberg (2007).
CD1 mediated T cell recognition of glycolipids.
  Curr Opin Struct Biol, 17, 521-529.  
17389239 N.Schrantz, Y.Sagiv, Y.Liu, P.B.Savage, A.Bendelac, and L.Teyton (2007).
The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells.
  J Exp Med, 204, 841-852.  
17006761 R.C.Halder, A.Jahng, I.Maricic, and V.Kumar (2007).
Mini review: immune response to myelin-derived sulfatide and CNS-demyelination.
  Neurochem Res, 32, 257-262.  
17641782 R.C.Halder, C.Aguilera, I.Maricic, and V.Kumar (2007).
Type II NKT cell-mediated anergy induction in type I NKT cells prevents inflammatory liver disease.
  J Clin Invest, 117, 2302-2312.  
16537470 D.Wu, D.M.Zajonc, M.Fujio, B.A.Sullivan, Y.Kinjo, M.Kronenberg, I.A.Wilson, and C.H.Wong (2006).
Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d.
  Proc Natl Acad Sci U S A, 103, 3972-3977.
PDB code: 2fik
17661645 G.Wingender, and M.Kronenberg (2006).
Invariant natural killer cells in the response to bacteria: the advent of specific antigens.
  Future Microbiol, 1, 325-340.  
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
16874306 L.F.Garcia-Alles, K.Versluis, L.Maveyraud, A.T.Vallina, S.Sansano, N.F.Bello, H.J.Gober, V.Guillet, H.de la Salle, G.Puzo, L.Mori, A.J.Heck, G.De Libero, and L.Mourey (2006).
Endogenous phosphatidylcholine and a long spacer ligand stabilize the lipid-binding groove of CD1b.
  EMBO J, 25, 3684-3692.
PDB code: 2h26
16936925 P.B.Savage, L.Teyton, and A.Bendelac (2006).
Glycolipids for natural killer T cells.
  Chem Soc Rev, 35, 771-779.  
16921381 Y.Kinjo, E.Tupin, D.Wu, M.Fujio, R.Garcia-Navarro, M.R.Benhnia, D.M.Zajonc, G.Ben-Menachem, G.D.Ainge, G.F.Painter, A.Khurana, K.Hoebe, S.M.Behar, B.Beutler, I.A.Wilson, M.Tsuji, T.J.Sellati, C.H.Wong, and M.Kronenberg (2006).
Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.
  Nat Immunol, 7, 978-986.  
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 codes are shown on the right.

 

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