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PDBsum entry 2q86
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Immune system PDB id
2q86

 

 

 

 

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Contents
Protein chains
189 a.a. *
233 a.a. *
Ligands
NAG-NAG-BMA-MAN-
FUC
NAG-NAG-BMA-FUC
NAG
Waters ×546
* Residue conservation analysis
PDB id:
2q86
Name: Immune system
Title: Structure of the mouse invariant nkt cell receptor valpha14
Structure: Valpha14 tcr. Chain: a, c. Fragment: extracellular domain. Engineered: yes. Mutation: yes. Vbeta8.2. Chain: b, d. Fragment: extracellular domain. Engineered: yes.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: valpha14. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Gene: vbeta8.2.
Resolution:
1.85Å     R-factor:   0.180     R-free:   0.223
Authors: D.M.Zajonc
Key ref:
D.M.Zajonc et al. (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. PubMed id: 18295796 DOI: 10.1016/j.jmb.2008.01.061
Date:
08-Jun-07     Release date:   01-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01849  (TCA_MOUSE) -  T-cell receptor alpha chain constant from Mus musculus
Seq:
Struc: 		136 a.a.
189 a.a.*
Protein chains
Pfam   ArchSchema ?
P01851  (TCB2_MOUSE) -  T-cell receptor beta-2 chain C region from Mus musculus
Seq:
Struc: 		173 a.a.
233 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1016/j.jmb.2008.01.061 J Mol Biol 377:1104-1116 (2008)
PubMed id: 18295796  
 
 
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.
D.M.Zajonc, P.B.Savage, A.Bendelac, I.A.Wilson, L.Teyton.
 
  ABSTRACT  
 
The semi-invariant Valpha14Jalpha18 T cell receptor (TCR) is expressed by regulatory NKT cells and has the unique ability to recognize chemically diverse ligands presented by CD1d. The crystal structure of CD1d complexed to a natural, endogenous ligand, isoglobotrihexosylceramide (iGb3), illustrates the extent of this diversity when compared to the binding of potent, exogenous ligands, such as alpha-galactosylceramide (alpha-GalCer). A single mode of recognition for these two classes of ligands would then appear problematic for a single T cell receptor. However, the Valpha14 TCR adopts two different conformations in the crystal where, in one configuration, the presence of a larger cavity between the two CDR3 regions could accommodate iGb3 and, in the other, a smaller cavity fits alpha-GalCer more snugly. Alternatively, the extended iGb3 headgroup could be "squashed" upon docking of the TCR and accommodated between the CD1 and TCR surfaces. Thus, the same TCR may adopt alternative modes of recognition for these foreign and self-ligands for NKT cell activation.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. A representation of the mCD1d-iGb3 complex (a) and chemical structures of CD1d ligands (b). a, The self-antigen iGb3 (yellow) is bound in the hydrophobic binding groove between the α1 and α2 helices of the CD1d heavy chain (grey) that associates non-covalently with β[2]-microblobulin (β[2]M, blue-grey) to form a biological heterodimer. Three of the four N-linked glycosylation sites (Asn20 (N20), Asn42 and Asn165) carry well-ordered carbohydrates (grey sticks). The spacer lipid (C[16], orange) present in the binding groove complements the short C[8]-alkyl chain of the synthetic ligand iGb3. b, The chemical structure of short-chain iGb3 is different from that of cis-tetracosenoyl sulfatide (sulfatide C[24:1]), which it resembles in the core structure, and the short-chain α-GalCer, which is dissimilar due to the different anomeric conformation of the galactose (α-versus β-glycosidic linkage). The terminal α1-3 linked galactose (red) is not ordered in the crystal structure and, therefore, not shown in Fig. 1 and Fig. 2). 		Figure 4.
Fig. 4. Low-affinity binding of CD1d-PBS-74 to recombinant TCR Vα14/2Cβ. (a) Successive dilutions of empty CD1d or CD1d-PBS-74 were injected over immobilized TCR. Subtraction (CD1-d-PBS-74 sensorgrams minus empty CD1 sensorgrams) and a 1:1 Langmuir fit of CD1d-PBS-74 binding are presented. (b) Magnified view of the dissociation phase comparing empty CD1d and CD1d-PBS-74. (c) Association constants of CD1d-PBS-25 and CD1d-PBS-74 for Vα14/2Cβ TCR. Measurements were reproduced in two separate experiments.
 
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 377, 1104-1116) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23154222 J.Rossjohn, D.G.Pellicci, O.Patel, L.Gapin, and D.I.Godfrey (2012).
Recognition of CD1d-restricted antigens by natural killer T cells.
  Nat Rev Immunol, 12, 845-857.  
21298486 E.Champagne (2011).
γδ T cell Receptor Ligands and Modes of Antigen Recognition.
  Arch Immunol Ther Exp (Warsz), 59, 117-137.  
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
19857519 G.De Libero, and L.Mori (2010).
How the immune system detects lipid antigens.
  Prog Lipid Res, 49, 120-127.  
20585371 G.Matulis, J.P.Sanderson, N.M.Lissin, M.B.Asparuhova, G.R.Bommineni, D.Schümperli, R.R.Schmidt, P.M.Villiger, B.K.Jakobsen, and S.D.Gadola (2010).
Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop.
  PLoS Biol, 8, e1000402.  
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
20407212 K.Yoshida, A.L.Corper, R.Herro, B.Jabri, I.A.Wilson, and L.Teyton (2010).
The diabetogenic mouse MHC class II molecule I-Ag7 is endowed with a switch that modulates TCR affinity.
  J Clin Invest, 120, 1578-1590.
PDB code: 3mbe
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.  
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.  
20616071 X.Li, M.Fujio, M.Imamura, D.Wu, S.Vasan, C.H.Wong, D.D.Ho, and M.Tsuji (2010).
Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant.
  Proc Natl Acad Sci U S A, 107, 13010-13015.  
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
19541469 A.Kasmar, I.Van Rhijn, and D.B.Moody (2009).
The evolved functions of CD1 during infection.
  Curr Opin Immunol, 21, 397-403.  
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
19968878 B.R.Dias, E.G.Rodrigues, L.Nimrichter, E.S.Nakayasu, I.C.Almeida, and L.R.Travassos (2009).
Identification of iGb3 and iGb4 in melanoma B16F10-Nex2 cells and the iNKT cell-mediated antitumor effect of dendritic cells primed with iGb3.
  Mol Cancer, 8, 116.  
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.  
19592275 D.G.Pellicci, O.Patel, L.Kjer-Nielsen, S.S.Pang, L.C.Sullivan, K.Kyparissoudis, A.G.Brooks, H.H.Reid, S.Gras, I.S.Lucet, R.Koh, M.J.Smyth, T.Mallevaey, J.L.Matsuda, L.Gapin, J.McCluskey, D.I.Godfrey, and J.Rossjohn (2009).
Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors.
  Immunity, 31, 47-59.
PDB codes: 3he6 3he7 3huj
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.  
  20948595 L.Teyton (2009).
Natural killer T cell recognition of lipid antigens.
  F1000 Biol Rep, 1, 0.  
19476512 M.Boes, A.J.Stoppelenburg, and F.C.Sillé (2009).
Endosomal processing for antigen presentation mediated by CD1 and Class I major histocompatibility complex: roads to display or destruction.
  Immunology, 127, 163-170.  
19627191 M.L.Lang (2009).
How do natural killer T cells help B cells?
  Expert Rev Vaccines, 8, 1109-1121.  
19592274 T.Mallevaey, J.P.Scott-Browne, J.L.Matsuda, M.H.Young, D.G.Pellicci, O.Patel, M.Thakur, L.Kjer-Nielsen, S.K.Richardson, V.Cerundolo, A.R.Howell, J.McCluskey, D.I.Godfrey, J.Rossjohn, P.Marrack, and L.Gapin (2009).
T cell receptor CDR2 beta and CDR3 beta loops collaborate functionally to shape the iNKT cell repertoire.
  Immunity, 31, 60-71.  
19079136 V.Cerundolo, J.D.Silk, S.H.Masri, and M.Salio (2009).
Harnessing invariant NKT cells in vaccination strategies.
  Nat Rev Immunol, 9, 28-38.  
19816402 W.C.Florence, C.Xia, L.E.Gordy, W.Chen, Y.Zhang, J.Scott-Browne, Y.Kinjo, K.O.Yu, S.Keshipeddy, D.G.Pellicci, O.Patel, L.Kjer-Nielsen, J.McCluskey, D.I.Godfrey, J.Rossjohn, S.K.Richardson, S.A.Porcelli, A.R.Howell, K.Hayakawa, L.Gapin, D.M.Zajonc, P.G.Wang, and S.Joyce (2009).
Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.
  EMBO J, 28, 3579-3590.  
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
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.  
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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