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PDBsum entry 2z35
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protein Protein-protein interface(s) links
Immune system PDB id
2z35

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
112 a.a. *
111 a.a. *
Waters ×25
* Residue conservation analysis
PDB id:
2z35
Name: Immune system
Title: Crystal structure of immune receptor
Structure: T-cell receptor alpha-chain. Chain: a. Engineered: yes. T-cell receptor beta-chain. Chain: b. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Resolution:
2.20Å     R-factor:   0.263     R-free:   0.285
Authors: D.Feng,C.J.Bond,L.K.Ely,K.C.Garcia
Key ref:
D.Feng et al. (2007). Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'. Nat Immunol, 8, 975-983. PubMed id: 17694060 DOI: 10.1038/ni1502
Date:
01-Jun-07     Release date:   09-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q5R1F5  (Q5R1F5_MOUSE) -  TRAV6D-7 (Fragment) from Mus musculus
Seq:
Struc: 		112 a.a.
112 a.a.*
Protein chain
Pfam   ArchSchema ?
A2NTY6  (A2NTY6_MOUSE) -  Beta-chain (Fragment) from Mus musculus
Seq:
Struc: 		144 a.a.
111 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 12 residue positions (black crosses)

 

 
DOI no: 10.1038/ni1502 Nat Immunol 8:975-983 (2007)
PubMed id: 17694060  
 
 
Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.
D.Feng, C.J.Bond, L.K.Ely, J.Maynard, K.C.Garcia.
 
  ABSTRACT  
 
All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable beta-chain 8.2 (V(beta)8.2), each bound to the MHC class II molecule I-A(u), and did energetic mapping of V(alpha) and V(beta) contacts with I-A(u). Together with two previously solved structures of V(beta)8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V(beta) loops and the I-A alpha-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.
 
  Selected figure(s)  
 
Figure 3.
(a) Structures of 1934.4, cl19 and 172.10 from TCR-pMHC complexes superimposed on I-A^u (colors as in Fig. 1). Red dashed lines, hydrogen bonds. (b) Interactions between TCR CDR1 and CDR2 loops and the I-A -helix. Highlighting indicates residues involved in interactions; black dashed lines, van der Waals forces; red dashed lines, hydrogen bonds. Top, interactions of 1934.4. 		Figure 5.
Yellow, peptide; red dashed lines, hydrogen bonds; black dashed lines, van der Waals interactions. TCR amino acids are designated by one-letter amino acid code followed by position number; peptide amino acids are designated by position (P) number, followed by the one-letter amino acid code. Below, two-dimensional projections of the CDR3-peptide contacts. (a) The 1934.4 complex. (b) The cl19 complex. (c) The 172.10 complex.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2007, 8, 975-983) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21199956 D.K.Sethi, D.A.Schubert, A.K.Anders, A.Heroux, D.A.Bonsor, C.P.Thomas, E.J.Sundberg, J.Pyrdol, and K.W.Wucherpfennig (2011).
A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC.
  J Exp Med, 208, 91.
PDB code: 3pl6
21321209 G.P.Morris, P.P.Ni, and P.M.Allen (2011).
Alloreactivity is limited by the endogenous peptide repertoire.
  Proc Natl Acad Sci U S A, 108, 3695-3700.  
21306912 K.W.Wucherpfennig, and D.Sethi (2011).
T cell receptor recognition of self and foreign antigens in the induction of autoimmunity.
  Semin Immunol, 23, 84-91.  
20931295 M.Cohn (2011).
On the logic of restrictive recognition of peptide by the T-cell antigen receptor.
  Immunol Res, 50, 49-68.  
  21301478 S.Gras, L.Kjer-Nielsen, Z.Chen, J.Rossjohn, and J.McCluskey (2011).
The structural bases of direct T-cell allorecognition: implications for T-cell-mediated transplant rejection.
  Immunol Cell Biol, 89, 388-395.  
21297580 Y.Yin, Y.Li, M.C.Kerzic, R.Martin, and R.A.Mariuzza (2011).
Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection.
  EMBO J, 30, 1137-1148.
PDB code: 3o6f
20644572 A.C.Carpenter, and R.Bosselut (2010).
Decision checkpoints in the thymus.
  Nat Immunol, 11, 666-673.  
20489610 A.W.Michels, and M.Nakayama (2010).
The anti-insulin trimolecular complex in type 1 diabetes.
  Curr Opin Endocrinol Diabetes Obes, 17, 329-334.  
20616723 C.T.Spencer, P.Gilchuk, S.M.Dragovic, and S.Joyce (2010).
Minor histocompatibility antigens: presentation principles, recognition logic and the potential for a healing hand.
  Curr Opin Organ Transplant, 15, 512-525.  
21173256 H.N.Eisen, and A.K.Chakraborty (2010).
Evolving concepts of specificity in immune reactions.
  Proc Natl Acad Sci U S A, 107, 22373-22380.  
20089450 J.D.Ahlers, and I.M.Belyakov (2010).
Lessons learned from natural infection: focusing on the design of protective T cell vaccines for HIV/AIDS.
  Trends Immunol, 31, 120-130.  
20457759 J.Juang, P.J.Ebert, D.Feng, K.C.Garcia, M.Krogsgaard, and M.M.Davis (2010).
Peptide-MHC heterodimers show that thymic positive selection requires a more restricted set of self-peptides than negative selection.
  J Exp Med, 207, 1223-1234.  
  20452950 K.W.Wucherpfennig, E.Gagnon, M.J.Call, E.S.Huseby, and M.E.Call (2010).
Structural biology of the T-cell receptor: insights into receptor assembly, ligand recognition, and initiation of signaling.
  Cold Spring Harb Perspect Biol, 2, a005140.  
20333301 M.A.Patarroyo, A.Bermúdez, C.López, G.Yepes, and M.E.Patarroyo (2010).
3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.
  PLoS One, 5, e9771.  
20616724 S.A.Leddon, and A.J.Sant (2010).
Generation of MHC class II-peptide ligands for CD4 T-cell allorecognition of MHC class II molecules.
  Curr Opin Organ Transplant, 15, 505-511.  
20690181 S.A.Valkenburg, E.B.Day, N.G.Swan, H.A.Croom, F.R.Carbone, P.C.Doherty, S.J.Turner, and K.Kedzierska (2010).
Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity for optimal TCR alpha beta pairing and function of virus-specific CD8+ T cells.
  Eur J Immunol, 40, 2470-2481.  
20566715 S.Gras, Z.Chen, J.J.Miles, Y.C.Liu, M.J.Bell, L.C.Sullivan, L.Kjer-Nielsen, R.M.Brennan, J.M.Burrows, M.A.Neller, R.Khanna, A.W.Purcell, A.G.Brooks, J.McCluskey, J.Rossjohn, and S.R.Burrows (2010).
Allelic polymorphism in the T cell receptor and its impact on immune responses.
  J Exp Med, 207, 1555-1567.
PDB codes: 3mv7 3mv8 3mv9
20483993 S.R.Burrows, Z.Chen, J.K.Archbold, F.E.Tynan, T.Beddoe, L.Kjer-Nielsen, J.J.Miles, R.Khanna, D.J.Moss, Y.C.Liu, S.Gras, L.Kostenko, R.M.Brennan, C.S.Clements, A.G.Brooks, A.W.Purcell, J.McCluskey, and J.Rossjohn (2010).
Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability.
  Proc Natl Acad Sci U S A, 107, 10608-10613.
PDB codes: 3kww 3kxf
19201651 A.Ziegler, C.A.Müller, R.A.Böckmann, and B.Uchanska-Ziegler (2009).
Low-affinity peptides and T-cell selection.
  Trends Immunol, 30, 53-60.  
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
19605354 D.K.Cole, F.Yuan, P.J.Rizkallah, J.J.Miles, E.Gostick, D.A.Price, G.F.Gao, B.K.Jakobsen, and A.K.Sewell (2009).
Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.
  J Biol Chem, 284, 27281-27289.
PDB code: 3hg1
  20948629 D.M.Kranz (2009).
Two mechanisms that account for major histocompatibility complex restriction of T cells.
  F1000 Biol Rep, 1, 0.  
19918786 J.A.Maynard, N.C.Lindquist, J.N.Sutherland, A.Lesuffleur, A.E.Warrington, M.Rodriguez, and S.H.Oh (2009).
Surface plasmon resonance for high-throughput ligand screening of membrane-bound proteins.
  Biotechnol J, 4, 1542-1558.  
19139173 J.K.Archbold, W.A.Macdonald, S.Gras, L.K.Ely, J.J.Miles, M.J.Bell, R.M.Brennan, T.Beddoe, M.C.Wilce, C.S.Clements, A.W.Purcell, J.McCluskey, S.R.Burrows, and J.Rossjohn (2009).
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
  J Exp Med, 206, 209-219.
PDB codes: 3dx6 3dx7 3dx8 3dx9 3dxa
19262510 J.P.Scott-Browne, J.White, J.W.Kappler, L.Gapin, and P.Marrack (2009).
Germline-encoded amino acids in the alphabeta T-cell receptor control thymic selection.
  Nature, 458, 1043-1046.  
19148199 K.C.Garcia, J.J.Adams, D.Feng, and L.K.Ely (2009).
The molecular basis of TCR germline bias for MHC is surprisingly simple.
  Nat Immunol, 10, 143-147.  
19416894 K.Rubtsova, J.P.Scott-Browne, F.Crawford, S.Dai, P.Marrack, and J.W.Kappler (2009).
Many different Vbeta CDR3s can reveal the inherent MHC reactivity of germline-encoded TCR V regions.
  Proc Natl Acad Sci U S A, 106, 7951-7956.  
19699075 K.W.Wucherpfennig, M.J.Call, L.Deng, and R.Mariuzza (2009).
Structural alterations in peptide-MHC recognition by self-reactive T cell receptors.
  Curr Opin Immunol, 21, 590-595.  
19464197 T.Beddoe, Z.Chen, C.S.Clements, L.K.Ely, S.R.Bushell, J.P.Vivian, L.Kjer-Nielsen, S.S.Pang, M.A.Dunstone, Y.C.Liu, W.A.Macdonald, M.A.Perugini, M.C.Wilce, S.R.Burrows, A.W.Purcell, T.Tiganis, S.P.Bottomley, J.McCluskey, and J.Rossjohn (2009).
Antigen ligation triggers a conformational change within the constant domain of the alphabeta T cell receptor.
  Immunity, 30, 777-788.  
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.  
19472182 Y.Chen, Y.Shi, H.Cheng, Y.Q.An, and G.F.Gao (2009).
Structural immunology and crystallography help immunologists see the immune system in action: how T and NK cells touch their ligands.
  IUBMB Life, 61, 579-590.  
18946038 A.Kosmrlj, A.K.Jha, E.S.Huseby, M.Kardar, and A.K.Chakraborty (2008).
How the thymus designs antigen-specific and self-tolerant T cell receptor sequences.
  Proc Natl Acad Sci U S A, 105, 16671-16676.  
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.  
18516039 E.J.Adams, P.Strop, S.Shin, Y.H.Chien, and K.C.Garcia (2008).
An autonomous CDR3delta is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by gammadelta T cells.
  Nat Immunol, 9, 777-784.  
18726714 E.J.Collins, and D.S.Riddle (2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
  Immunol Res, 41, 267-294.  
18275824 J.H.Wang, R.J.Mallis, and E.L.Reinherz (2008).
Immunodominant-peptide recognition: beta testing TCRalphabeta.
  Immunity, 28, 139-141.  
18378495 J.K.Archbold, W.A.Macdonald, S.R.Burrows, J.Rossjohn, and J.McCluskey (2008).
T-cell allorecognition: a case of mistaken identity or déjà vu?
  Trends Immunol, 29, 220-226.  
18800968 K.M.Armstrong, K.H.Piepenbrink, and B.M.Baker (2008).
Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes.
  Biochem J, 415, 183-196.  
18378792 K.S.Wun, N.A.Borg, L.Kjer-Nielsen, T.Beddoe, R.Koh, S.K.Richardson, M.Thakur, A.R.Howell, J.P.Scott-Browne, L.Gapin, D.I.Godfrey, J.McCluskey, and J.Rossjohn (2008).
A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR.
  J Exp Med, 205, 939-949.  
18678247 L.K.Ely, S.R.Burrows, A.W.Purcell, J.Rossjohn, and J.McCluskey (2008).
T-cells behaving badly: structural insights into alloreactivity and autoimmunity.
  Curr Opin Immunol, 20, 575-580.  
  18941216 L.L.Jones, L.A.Colf, J.D.Stone, K.C.Garcia, and D.M.Kranz (2008).
Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation.
  J Immunol, 181, 6255-6264.
PDB codes: 3e2h 3e3q
18394705 M.Cohn (2008).
What does the T-cell receptor recognize when it docks on an MHC-encoded restricting element?
  Mol Immunol, 45, 3264-3267.  
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.  
18456484 P.Marrack, K.Rubtsova, J.Scott-Browne, and J.W.Kappler (2008).
T cell receptor specificity for major histocompatibility complex proteins.
  Curr Opin Immunol, 20, 203-207.  
18308592 S.Dai, E.S.Huseby, K.Rubtsova, J.Scott-Browne, F.Crawford, W.A.Macdonald, P.Marrack, and J.W.Kappler (2008).
Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules.
  Immunity, 28, 324-334.
PDB codes: 3c5z 3c60 3c6l
18207719 S.Gras, L.Kjer-Nielsen, S.R.Burrows, J.McCluskey, and J.Rossjohn (2008).
T-cell receptor bias and immunity.
  Curr Opin Immunol, 20, 119-125.  
18703505 T.Mareeva, E.Martinez-Hackert, and Y.Sykulev (2008).
How a T cell receptor-like antibody recognizes major histocompatibility complex-bound peptide.
  J Biol Chem, 283, 29053-29059.
PDB codes: 3cvh 3cvi
18007679 N.J.Felix, and P.M.Allen (2007).
Specificity of T-cell alloreactivity.
  Nat Rev Immunol, 7, 942-953.  
17925433 W.W.Schamel, and M.Reth (2007).
The TCR binding site does move.
  Proc Natl Acad Sci U S A, 104, 16398-16399.  
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.

 

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