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PDBsum entry 1bx2

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protein ligands Protein-protein interface(s) links
Immune system PDB id
1bx2
Jmol
Contents
Protein chains
180 a.a. *
191 a.a. *
14 a.a. *
14 a.a. *
Ligands
NAG ×2
Waters ×48
* Residue conservation analysis
PDB id:
1bx2
Name: Immune system
Title: Crystal structure of hla-dr2 (dra 0101,Drb1 1501) Complexed peptide from human myelin basic protein
Structure: Protein (hla-dr2). Chain: a, d. Fragment: extracellular domains alpha 1, alpha 2. Engineered: yes. Protein (hla-dr2). Chain: b, e. Fragment: extracellular domains beta 1, beta 2. Protein (hla-dr2). Chain: c, f.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469. Other_details: myelin basic protein peptide was covalently the n-terminus of the hla-dr2 beta chain
Biol. unit: Hexamer (from PQS)
Resolution:
2.60Å     R-factor:   0.238     R-free:   0.266
Authors: K.J.Smith,J.Pyrdol,L.Gauthier,D.C.Wiley,K.Wucherpfennig
Key ref: K.J.Smith et al. (1998). Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein. J Exp Med, 188, 1511-1520. PubMed id: 9782128
Date:
12-Oct-98     Release date:   21-Oct-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
Seq:
Struc:
254 a.a.
180 a.a.
Protein chains
Pfam   ArchSchema ?
P01911  (2B1F_HUMAN) -  HLA class II histocompatibility antigen, DRB1-15 beta chain
Seq:
Struc:
266 a.a.
191 a.a.
Protein chain
Pfam   ArchSchema ?
P02686  (MBP_HUMAN) -  Myelin basic protein
Seq:
Struc:
304 a.a.
14 a.a.
Protein chain
Pfam   ArchSchema ?
P02686  (MBP_HUMAN) -  Myelin basic protein
Seq:
Struc:
304 a.a.
14 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 
  Biochemical function     structural constituent of myelin sheath     1 term  

 

 
J Exp Med 188:1511-1520 (1998)
PubMed id: 9782128  
 
 
Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein.
K.J.Smith, J.Pyrdol, L.Gauthier, D.C.Wiley, K.W.Wucherpfennig.
 
  ABSTRACT  
 
Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent, solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DRbeta 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.
 

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
20736999 J.Huan, R.Meza-Romero, J.L.Mooney, A.A.Vandenbark, H.Offner, and G.G.Burrows (2011).
Single-chain recombinant HLA-DQ2.5/peptide molecules block α2-gliadin-specific pathogenic CD4+ T-cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease.
  Mucosal Immunol, 4, 112-120.  
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.  
  21469129 R.Dahan, M.Tabul, Y.K.Chou, R.Meza-Romero, S.Andrew, A.J.Ferro, G.G.Burrows, H.Offner, A.A.Vandenbark, and Y.Reiter (2011).
TCR-like antibodies distinguish conformational and functional differences in two- versus four-domain auto reactive MHC class II-peptide complexes.
  Eur J Immunol, 41, 1465-1479.  
21116684 Zaheer-ul-Haq, and W.Khan (2011).
Molecular and structural determinants of adamantyl susceptibility to HLA-DRs allelic variants: an in silico approach to understand the mechanism of MLEs.
  J Comput Aided Mol Des, 25, 81.  
19933168 D.R.Karp, N.Marthandan, S.G.Marsh, C.Ahn, F.C.Arnett, D.S.Deluca, A.D.Diehl, R.Dunivin, K.Eilbeck, M.Feolo, P.A.Guidry, W.Helmberg, S.Lewis, M.D.Mayes, C.Mungall, D.A.Natale, B.Peters, E.Petersdorf, J.D.Reveille, B.Smith, G.Thomson, M.J.Waller, and R.H.Scheuermann (2010).
Novel sequence feature variant type analysis of the HLA genetic association in systemic sclerosis.
  Hum Mol Genet, 19, 707-719.  
20122230 K.Yeturu, T.Utriainen, G.J.Kemp, and N.Chandra (2010).
An automated framework for understanding structural variations in the binding grooves of MHC class II molecules.
  BMC Bioinformatics, 11, S55.  
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
19414787 M.J.Call, X.Xing, G.D.Cuny, N.P.Seth, D.M.Altmann, L.Fugger, M.Krogsgaard, R.L.Stein, and K.W.Wucherpfennig (2009).
In vivo enhancement of peptide display by MHC class II molecules with small molecule catalysts of peptide exchange.
  J Immunol, 182, 6342-6352.  
19132105 W.A.Agudelo, J.F.Galindo, M.Ortiz, J.L.Villaveces, E.E.Daza, and M.E.Patarroyo (2009).
Variations in the electrostatic landscape of class II human leukocyte antigen molecule induced by modifications in the myelin basic protein peptide: a theoretical approach.
  PLoS ONE, 4, e4164.  
18525076 B.A.Cobb, and D.L.Kasper (2008).
Characteristics of carbohydrate antigen binding to the presentation protein HLA-DR.
  Glycobiology, 18, 707-718.  
18854049 C.S.Parry, and B.R.Brooks (2008).
A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes.
  Biol Direct, 3, 42.  
18542080 J.R.Oksenberg, S.E.Baranzini, S.Sawcer, and S.L.Hauser (2008).
The genetics of multiple sclerosis: SNPs to pathways to pathogenesis.
  Nat Rev Genet, 9, 516-526.  
17559577 C.E.Voorter, M.Amicosante, F.Berretta, L.Groeneveld, M.Drent, and E.M.van den Berg-Loonen (2007).
HLA class II amino acid epitopes as susceptibility markers of sarcoidosis.
  Tissue Antigens, 70, 18-27.  
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.  
17803448 H.Albrecht, M.Cosman, M.Ngu-Schwemlein, M.Corzett, K.W.Curran, C.Dolan, X.Fang, S.J.DeNardo, G.L.DeNardo, and R.Balhorn (2007).
Recombinant expression of the beta-subunit of HLA-DR10 for the selection of novel lymphoma targeting molecules.
  Cancer Biother Radiopharm, 22, 531-542.  
16990347 L.S.Kreisman, J.H.Friedman, A.Neaga, and B.A.Cobb (2007).
Structure and function relations with a T-cell-activating polysaccharide antigen using circular dichroism.
  Glycobiology, 17, 46-55.  
17207708 R.J.Duquesnoy, and M.Askar (2007).
HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP.
  Hum Immunol, 68, 12-25.  
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.  
  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.  
15915462 A.Godkin, M.Davenport, and A.V.Hill (2005).
Molecular analysis of HLA class II associations with hepatitis B virus clearance and vaccine nonresponsiveness.
  Hepatology, 41, 1383-1390.  
16026228 D.M.Mezzapesa, M.Rovaris, and M.Filippi (2005).
Glatiramer acetate in multiple sclerosis.
  Expert Rev Neurother, 5, 451-458.  
15711804 H.Duyar, J.Dengjel, K.L.de Graaf, K.H.Wiesmüller, S.Stevanović, and R.Weissert (2005).
Peptide motif for the rat MHC class II molecule RT1.Da: similarities to the multiple sclerosis-associated HLA-DRB1*1501 molecule.
  Immunogenetics, 57, 69-76.  
15834022 J.M.Greer, and M.P.Pender (2005).
The presence of glutamic acid at positions 71 or 74 in pocket 4 of the HLA-DRbeta1 chain is associated with the clinical course of multiple sclerosis.
  J Neurol Neurosurg Psychiatry, 76, 656-662.  
15665083 J.N.Stern, Z.Illés, J.Reddy, D.B.Keskin, M.Fridkis-Hareli, V.K.Kuchroo, and J.L.Strominger (2005).
Peptide 15-mers of defined sequence that substitute for random amino acid copolymers in amelioration of experimental autoimmune encephalomyelitis.
  Proc Natl Acad Sci U S A, 102, 1620-1625.  
15973459 J.R.Oksenberg, and L.F.Barcellos (2005).
Multiple sclerosis genetics: leaving no stone unturned.
  Genes Immun, 6, 375-387.  
15661088 J.R.Oksenberg, and S.L.Hauser (2005).
Genetics of multiple sclerosis.
  Neurol Clin, 23, 61.  
16098233 M.Amicosante, F.Berretta, M.Rossman, R.H.Butler, P.Rogliani, E.van den Berg-Loonen, and C.Saltini (2005).
Identification of HLA-DRPhebeta47 as the susceptibility marker of hypersensitivity to beryllium in individuals lacking the berylliosis-associated supratypic marker HLA-DPGlubeta69.
  Respir Res, 6, 94.  
16318989 P.Fontoura, H.Garren, and L.Steinman (2005).
Antigen-specific therapies in multiple sclerosis: going beyond proteins and peptides.
  Int Rev Immunol, 24, 415-446.  
16079912 Y.Li, Y.Huang, J.Lue, J.A.Quandt, R.Martin, and R.A.Mariuzza (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.
PDB code: 1zgl
15291817 A.G.Tzakos, P.Fuchs, N.A.van Nuland, A.Troganis, T.Tselios, S.Deraos, J.Matsoukas, I.P.Gerothanassis, and A.M.Bonvin (2004).
NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist: structural implications for the MHC II (I-Au)-peptide complex from docking calculations.
  Eur J Biochem, 271, 3399-3413.  
15020763 C.Y.Kim, H.Quarsten, E.Bergseng, C.Khosla, and L.M.Sollid (2004).
Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease.
  Proc Natl Acad Sci U S A, 101, 4175-4179.
PDB code: 1s9v
14748001 H.D.Schafroth, and C.A.Floudas (2004).
Predicting peptide binding to MHC pockets via molecular modeling, implicit solvation, and global optimization.
  Proteins, 54, 534-556.  
15292514 J.N.Stern, Z.Illés, J.Reddy, D.B.Keskin, E.Sheu, M.Fridkis-Hareli, H.Nishimura, C.F.Brosnan, L.Santambrogio, V.K.Kuchroo, and J.L.Strominger (2004).
Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms.
  Proc Natl Acad Sci U S A, 101, 11743-11748.  
14669136 J.R.Oksenberg, L.F.Barcellos, B.A.Cree, S.E.Baranzini, T.L.Bugawan, O.Khan, R.R.Lincoln, A.Swerdlin, E.Mignot, L.Lin, D.Goodin, H.A.Erlich, S.Schmidt, G.Thomson, D.E.Reich, M.A.Pericak-Vance, J.L.Haines, and S.L.Hauser (2004).
Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans.
  Am J Hum Genet, 74, 160-167.  
15102570 J.S.Wolinsky (2004).
Glatiramer acetate for the treatment of multiple sclerosis.
  Expert Opin Pharmacother, 5, 875-891.  
15372502 T.P.Finn, R.E.Jones, C.Rich, R.Dahan, J.Link, C.S.David, Y.K.Chou, H.Offner, and A.A.Vandenbark (2004).
HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes.
  J Neurosci Res, 78, 100-114.  
14743435 Y.K.Chou, G.G.Burrows, D.LaTocha, C.Wang, S.Subramanian, D.N.Bourdette, and A.A.Vandenbark (2004).
CD4 T-cell epitopes of human alpha B-crystallin.
  J Neurosci Res, 75, 516-523.  
15292513 Z.Illés, J.N.Stern, J.Reddy, H.Waldner, M.P.Mycko, C.F.Brosnan, S.Ellmerich, D.M.Altmann, L.Santambrogio, J.L.Strominger, and V.K.Kuchroo (2004).
Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells.
  Proc Natl Acad Sci U S A, 101, 11749-11754.  
15331779 Z.Zavala-Ruiz, I.Strug, B.D.Walker, P.J.Norris, and L.J.Stern (2004).
A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition.
  Proc Natl Acad Sci U S A, 101, 13279-13284.
PDB codes: 1sje 1sjh
12694585 E.Quelvennec, O.Bera, P.Cabre, M.Alizadeh, D.Smadja, F.Jugde, G.Edan, and G.Semana (2003).
Genetic and functional studies in multiple sclerosis patients from Martinique attest for a specific and direct role of the HLA-DR locus in the syndrome.
  Tissue Antigens, 61, 166-171.  
12557126 L.F.Barcellos, J.R.Oksenberg, A.B.Begovich, E.R.Martin, S.Schmidt, E.Vittinghoff, D.S.Goodin, D.Pelletier, R.R.Lincoln, P.Bucher, A.Swerdlin, M.A.Pericak-Vance, J.L.Haines, and S.L.Hauser (2003).
HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course.
  Am J Hum Genet, 72, 710-716.  
  12234092 D.S.Libich, and G.Harauz (2002).
Interactions of the 18.5-kDa isoform of myelin basic protein with Ca(2+)-calmodulin: in vitro studies using fluorescence microscopy and spectroscopy.
  Biochem Cell Biol, 80, 395-406.  
11790531 E.J.Sundberg, Y.Li, and R.A.Mariuzza (2002).
So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes.
  Curr Opin Immunol, 14, 36-44.  
12067291 E.Meinl, and R.Hohlfeld (2002).
Immunopathogenesis of multiple sclerosis: MBP and beyond.
  Clin Exp Immunol, 128, 395-397.  
12010576 P.E.Adrian, G.Rajaseger, V.S.Mathura, M.K.Sakharkar, and P.Kangueane (2002).
Types of inter-atomic interactions at the MHC-peptide interface: identifying commonality from accumulated data.
  BMC Struct Biol, 2, 2.  
12150894 X.L.He, C.Radu, J.Sidney, A.Sette, E.S.Ward, and K.C.Garcia (2002).
Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au.
  Immunity, 17, 83-94.
PDB code: 1k2d
12084926 X.Liu, S.Dai, F.Crawford, R.Fruge, P.Marrack, and J.Kappler (2002).
Alternate interactions define the binding of peptides to the MHC molecule IA(b).
  Proc Natl Acad Sci U S A, 99, 8820-8825.
PDB code: 1lnu
11498300 B.E.Gewurz, R.Gaudet, D.Tortorella, E.W.Wang, and H.L.Ploegh (2001).
Virus subversion of immunity: a structural perspective.
  Curr Opin Immunol, 13, 442-450.  
11433380 C.Texier, S.Pouvelle-Moratille, M.Busson, D.Charron, A.Ménez, and B.Maillère (2001).
Complementarity and redundancy of the binding specificity of HLA-DRB1, -DRB3, -DRB4 and -DRB5 molecules.
  Eur J Immunol, 31, 1837-1846.  
11580857 H.A.Elsner, K.Kotsch, and R.Blasczyk (2001).
Identification of the novel allele HLA-DRB1*1137 which probably originated from DRB1*11011: implications for mismatch with its ancestor allele at bone marrow transplantation.
  Tissue Antigens, 58, 47-49.  
  11602615 K.W.Wucherpfennig (2001).
Mechanisms for the induction of autoimmunity by infectious agents.
  J Clin Invest, 108, 1097-1104.  
11334495 K.W.Wucherpfennig (2001).
Structural basis of molecular mimicry.
  J Autoimmun, 16, 293-302.  
11556969 M.Minohara, H.Ochi, S.Matsushita, A.Irie, Y.Nishimura, and J.Kira (2001).
Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls.
  Tissue Antigens, 57, 447-456.  
  11890612 S.Casares, C.A.Bona, and T.D.Brumeanu (2001).
Modulation of CD4 T cell function by soluble MHC II-peptide chimeras.
  Int Rev Immunol, 20, 547-573.  
11053110 A.Simon, Z.Dosztányi, E.Rajnavölgyi, and I.Simon (2000).
Function-related regulation of the stability of MHC proteins.
  Biophys J, 79, 2305-2313.  
10841661 K.Kawamura, T.Yamamura, K.Yokoyama, D.H.Chui, Y.Fukui, T.Sasazuki, H.Inoko, C.S.David, and T.Tabira (2000).
Hla-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice.
  J Clin Invest, 105, 977-984.  
10882053 L.Steinman (2000).
Despite epitope spreading in the pathogenesis of autoimmune disease, highly restricted approaches to immune therapy may still succeed [with a hedge on this bet].
  J Autoimmun, 14, 278-282.  
10770805 M.Krogsgaard, K.W.Wucherpfennig, B.Cannella, B.E.Hansen, A.Svejgaard, J.Pyrdol, H.Ditzel, C.Raine, J.Engberg, L.Fugger, and B.Canella (2000).
Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex.
  J Exp Med, 191, 1395-1412.  
10756085 N.Abiru, D.Wegmann, E.Kawasaki, P.Gottlieb, E.Simone, and G.S.Eisenbarth (2000).
Dual overlapping peptides recognized by insulin peptide B:9-23 T cell receptor AV13S3 T cell clones of the NOD mouse.
  J Autoimmun, 14, 231-237.  
10894169 R.R.Latek, A.Suri, S.J.Petzold, C.A.Nelson, O.Kanagawa, E.R.Unanue, and D.H.Fremont (2000).
Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.
  Immunity, 12, 699-710.
PDB code: 1f3j
10607669 K.Maenaka, and E.Y.Jones (1999).
MHC superfamily structure and the immune system.
  Curr Opin Struct Biol, 9, 745-753.  
10190892 L.Steinman (1999).
Absence of "original antigenic sin" in autoimmunity provides an unforeseen platform for immune therapy.
  J Exp Med, 189, 1021-1024.  
10209044 P.J.Ruiz, H.Garren, D.L.Hirschberg, A.M.Langer-Gould, M.Levite, M.V.Karpuj, S.Southwood, A.Sette, P.Conlon, and L.Steinman (1999).
Microbial epitopes act as altered peptide ligands to prevent experimental autoimmune encephalomyelitis.
  J Exp Med, 189, 1275-1284.  
10571772 R.G.Phelps, and A.J.Rees (1999).
The HLA complex in Goodpasture's disease: a model for analyzing susceptibility to autoimmunity.
  Kidney Int, 56, 1638-1653.  
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.