PDBsum entry 1zgl

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protein Protein-protein interface(s) links
Immune system PDB id
Protein chains
178 a.a. *
175 a.a. *
14 a.a. *
178 a.a. *
242 a.a. *
175 a.a. *
15 a.a. *
187 a.a. *
13 a.a. *
176 a.a. *
226 a.a. *
180 a.a. *
195 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of 3a6 tcr bound to mbp/hla-dr2a
Structure: Hla class ii histocompatibility antigen, dr alpha chain. Chain: a, d, g, j. Fragment: 3a6. Synonym: mhc class ii antigen dra. Engineered: yes. Major histocompatibility complex, class ii, dr beta 5. Chain: b, e, h, k.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthesized mbp residues 87-99.
Biol. unit: Not given
2.80Å     R-factor:   0.280     R-free:   0.329
Authors: Y.Li,Y.Huang,J.Lue,J.A.Quandt,R.Martin,R.A.Mariuzza
Key ref:
Y.Li et al. (2005). Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. EMBO J, 24, 2968-2979. PubMed id: 16079912 DOI: 10.1038/sj.emboj.7600771
21-Apr-05     Release date:   18-Oct-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
254 a.a.
178 a.a.
Protein chain
Pfam   ArchSchema ?
Q30154  (DRB5_HUMAN) -  HLA class II histocompatibility antigen, DR beta 5 chain
266 a.a.
175 a.a.
Protein chains
Pfam   ArchSchema ?
P02686  (MBP_HUMAN) -  Myelin basic protein
304 a.a.
14 a.a.*
Protein chain
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T-cell receptor alpha chain C region
142 a.a.
178 a.a.*
Protein chains
Pfam   ArchSchema ?
P01850  (TRBC1_HUMAN) -  T-cell receptor beta-1 chain C region
177 a.a.
242 a.a.*
Protein chains
Pfam   ArchSchema ?
Q30154  (DRB5_HUMAN) -  HLA class II histocompatibility antigen, DR beta 5 chain
266 a.a.
175 a.a.
Protein chain
Pfam   ArchSchema ?
P02686  (MBP_HUMAN) -  Myelin basic protein
304 a.a.
15 a.a.*
Protein chain
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T-cell receptor alpha chain C region
142 a.a.
187 a.a.*
Protein chain
Pfam   ArchSchema ?
P02686  (MBP_HUMAN) -  Myelin basic protein
304 a.a.
13 a.a.*
Protein chain
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T-cell receptor alpha chain C region
142 a.a.
176 a.a.*
Protein chain
Pfam   ArchSchema ?
P01850  (TRBC1_HUMAN) -  T-cell receptor beta-1 chain C region
177 a.a.
226 a.a.*
Protein chain
Pfam   ArchSchema ?
Q30154  (DRB5_HUMAN) -  HLA class II histocompatibility antigen, DR beta 5 chain
266 a.a.
180 a.a.
Protein chain
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T-cell receptor alpha chain C region
142 a.a.
195 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 24 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 


DOI no: 10.1038/sj.emboj.7600771 EMBO J 24:2968-2979 (2005)
PubMed id: 16079912  
Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
Y.Li, Y.Huang, J.Lue, J.A.Quandt, R.Martin, R.A.Mariuzza.
Multiple sclerosis is mediated by T-cell responses to central nervous system antigens such as myelin basic protein (MBP). To investigate self-peptide/major histocompatibility complex (MHC) recognition and T-cell receptor (TCR) degeneracy, we determined the crystal structure, at 2.8 A resolution, of an autoimmune TCR (3A6) bound to an MBP self-peptide and the multiple sclerosis-associated MHC class II molecule, human leukocyte antigen (HLA)-DR2a. The complex reveals that 3A6 primarily recognizes the N-terminal portion of MBP, in contrast with antimicrobial and alloreactive TCRs, which focus on the peptide center. Moreover, this binding mode, which may be frequent among autoimmune TCRs, is compatible with a wide range of orientation angles of TCR to peptide/MHC. The interface is characterized by a scarcity of hydrogen bonds between TCR and peptide, and TCR-induced conformational changes in MBP/HLA-DR2a, which likely explain the low observed affinity. Degeneracy of 3A6, manifested by recognition of superagonist peptides bearing substitutions at nearly all TCR-contacting positions, results from the few specific interactions between 3A6 and MBP, allowing optimization of interface complementarity through variations in the peptide.
  Selected figure(s)  
Figure 2.
Figure 2 Electron density in the interface of the 3A6/MBP/HLA-DR2a complex. Density from the final 2F[o]-F[c] map at 2.8 resolution showing the N-terminal region of the MBP peptide. TCR is yellow, peptide is red and MHC is cyan. Contours are at 1 .
Figure 4.
Figure 4 Interactions of TCR 3A6 with HLA-DR2a and the MBP peptide. (A) Interactions of the HLA-DR2a -chains (cyan) and -chains (green) with the TCR 3A6 -chains (yellow) and -chains (gray). The contact residues are drawn and labeled. Hydrogen bonds are indicated by broken black lines and the MBP peptide is magenta. (B) Interactions of the TCR 3A6 -chains (yellow) and -chains (gray) with the MBP peptide (magenta) drawn in a ball-and-stick representation. Contact residues are labeled. The P2 Lys N -O CDR3 Gly94 hydrogen bond is present in only two of the four complex molecules in the asymmetric unit of the crystal.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 2968-2979) copyright 2005.  
  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
21364947 J.M.Khan, and S.Ranganathan (2011).
Understanding TR Binding to pMHC Complexes: How Does a TR Scan Many pMHC Complexes yet Preferentially Bind to One.
  PLoS One, 6, e17194.  
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.  
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
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.  
20534455 B.D.Stadinski, L.Zhang, F.Crawford, P.Marrack, G.S.Eisenbarth, and J.W.Kappler (2010).
Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register.
  Proc Natl Acad Sci U S A, 107, 10978-10983.  
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.  
20644721 M.C.De Rosa, B.Giardina, C.Bianchi, C.Carelli Alinovi, D.Pirolli, G.Ferraccioli, M.De Santis, G.Di Sante, and F.Ria (2010).
Modeling the ternary complex TCR-Vbeta/CollagenII(261-273)/HLA-DR4 associated with rheumatoid arthritis.
  PLoS One, 5, e11550.  
21115828 S.Günther, A.Schlundt, J.Sticht, Y.Roske, U.Heinemann, K.H.Wiesmüller, G.Jung, K.Falk, O.Rötzschke, and C.Freund (2010).
Bidirectional binding of invariant chain peptides to an MHC class II molecule.
  Proc Natl Acad Sci U S A, 107, 22219-22224.
PDB codes: 3pdo 3pgc 3pgd
20334923 S.P.Persaud, D.L.Donermeyer, K.S.Weber, D.M.Kranz, and P.M.Allen (2010).
High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
  Mol Immunol, 47, 1793-1801.  
19125887 J.D.Stone, A.S.Chervin, and D.M.Kranz (2009).
T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity.
  Immunology, 126, 165-176.  
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.  
19303388 M.Harkiolaki, S.L.Holmes, P.Svendsen, J.W.Gregersen, L.T.Jensen, R.McMahon, M.A.Friese, G.van Boxel, R.Etzensperger, J.S.Tzartos, K.Kranc, S.Sainsbury, K.Harlos, E.D.Mellins, J.Palace, M.M.Esiri, P.A.van der Merwe, E.Y.Jones, and L.Fugger (2009).
T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.
  Immunity, 30, 348-357.
PDB code: 2wbj
20064442 Y.Yin, and R.A.Mariuzza (2009).
The multiple mechanisms of T cell receptor cross-reactivity.
  Immunity, 31, 849-851.  
18155234 C.McBeth, A.Seamons, J.C.Pizarro, S.J.Fleishman, D.Baker, T.Kortemme, J.M.Goverman, and R.K.Strong (2008).
A new twist in TCR diversity revealed by a forbidden alphabeta TCR.
  J Mol Biol, 375, 1306-1319.
PDB codes: 2p1y 2p24
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.  
18207413 E.D.Mantzourani, K.Blokar, T.V.Tselios, J.M.Matsoukas, J.A.Platts, T.M.Mavromoustakos, and S.G.Grdadolnik (2008).
A combined NMR and molecular dynamics simulation study to determine the conformational properties of agonists and antagonists against experimental autoimmune encephalomyelitis.
  Bioorg Med Chem, 16, 2171-2182.  
18726714 E.J.Collins, and D.S.Riddle (2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
  Immunol Res, 41, 267-294.  
  18713991 K.Kawamura, K.A.McLaughlin, R.Weissert, and T.G.Forsthuber (2008).
Myelin-reactive type B T cells and T cells specific for low-affinity MHC-binding myelin peptides escape tolerance in HLA-DR transgenic mice.
  J Immunol, 181, 3202-3211.  
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.  
18157812 L.G.Petrich de Marquesini, A.K.Moustakas, I.J.Thomas, L.Wen, G.K.Papadopoulos, and F.S.Wong (2008).
Functional inhibition related to structure of a highly potent insulin-specific CD8 T cell clone using altered peptide ligands.
  Eur J Immunol, 38, 240-249.  
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
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.  
18513924 R.Etzensperger, R.M.McMahon, E.Y.Jones, and L.Fugger (2008).
Dissection of the multiple sclerosis associated DR2 haplotype.
  J Autoimmun, 31, 201-207.  
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
18824684 Z.Kato, J.N.Stern, H.K.Nakamura, K.Kuwata, N.Kondo, and J.L.Strominger (2008).
Positioning of autoimmune TCR-Ob.2F3 and TCR-Ob.3D1 on the MBP85-99/HLA-DR2 complex.
  Proc Natl Acad Sci U S A, 105, 15523-15528.  
17521918 C.Mazza, and B.Malissen (2007).
What guides MHC-restricted TCR recognition?
  Semin Immunol, 19, 225-235.  
17657565 E.Evensen, D.Joseph-McCarthy, G.A.Weiss, S.L.Schreiber, and M.Karplus (2007).
Ligand design by a combinatorial approach based on modeling and experiment: application to HLA-DR4.
  J Comput Aided Mol Des, 21, 395-418.  
17560120 E.J.Sundberg, L.Deng, and R.A.Mariuzza (2007).
TCR recognition of peptide/MHC class II complexes and superantigens.
  Semin Immunol, 19, 262-271.  
17304631 G.Cai, and D.A.Hafler (2007).
Multispecific responses by T cells expanded by endogenous self-peptide/MHC complexes.
  Eur J Immunol, 37, 602-612.  
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.  
17950605 L.Deng, and R.A.Mariuzza (2007).
Recognition of self-peptide-MHC complexes by autoimmune T-cell receptors.
  Trends Biochem Sci, 32, 500-508.  
17334368 L.Deng, R.J.Langley, P.H.Brown, G.Xu, L.Teng, Q.Wang, M.I.Gonzales, G.G.Callender, M.I.Nishimura, S.L.Topalian, and R.A.Mariuzza (2007).
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.
  Nat Immunol, 8, 398-408.
PDB codes: 2ial 2iam 2ian
17560605 S.Günther, A.K.Varma, B.Moza, K.J.Kasper, A.W.Wyatt, P.Zhu, A.K.Rahman, Y.Li, R.A.Mariuzza, J.K.McCormick, and E.J.Sundberg (2007).
A novel loop domain in superantigens extends their T cell receptor recognition site.
  J Mol Biol, 371, 210-221.
PDB codes: 2nts 2ntt
16537438 A.A.Musse, J.M.Boggs, and G.Harauz (2006).
Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope.
  Proc Natl Acad Sci U S A, 103, 4422-4427.  
16420483 C.Farès, D.S.Libich, and G.Harauz (2006).
Solution NMR structure of an immunodominant epitope of myelin basic protein. Conformational dependence on environment of an intrinsically unstructured protein.
  FEBS J, 273, 601-614.  
16407132 C.P.Swaminathan, P.H.Brown, A.Roychowdhury, Q.Wang, R.Guan, N.Silverman, W.E.Goldman, G.J.Boons, and R.A.Mariuzza (2006).
Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs).
  Proc Natl Acad Sci U S A, 103, 684-689.  
16557259 E.Y.Jones, L.Fugger, J.L.Strominger, and C.Siebold (2006).
MHC class II proteins and disease: a structural perspective.
  Nat Rev Immunol, 6, 271-282.  
16518843 M.C.Alcaro, and A.M.Papini (2006).
Contribution of peptides to multiple sclerosis research.
  Biopolymers, 84, 349-367.  
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.  
16829512 M.M.Fernández, R.Guan, C.P.Swaminathan, E.L.Malchiodi, and R.A.Mariuzza (2006).
Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule.
  J Biol Chem, 281, 25356-25364.
PDB code: 2g9h
  16424227 M.Sospedra, P.A.Muraro, I.Stefanová, Y.Zhao, K.Chung, Y.Li, M.Giulianotti, R.Simon, R.Mariuzza, C.Pinilla, and R.Martin (2006).
Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the multiple sclerosis-associated HLA-DR2 haplotype.
  J Immunol, 176, 1951-1961.  
17010587 M.Sospedra, and R.Martin (2006).
When T cells recognize a pattern, they might cause trouble.
  Curr Opin Immunol, 18, 697-703.  
16618592 R.A.Mariuzza (2006).
Multiple paths to multispecificity.
  Immunity, 24, 359-361.
PDB codes: 2a6d 2a6i 2a6j 2a6k
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
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.