PDBsum entry 1aqd

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protein Protein-protein interface(s) links
Complex (mhc protein/antigen) PDB id
Protein chains
179 a.a. *
187 a.a. *
14 a.a. *
13 a.a. *
Waters ×152
* Residue conservation analysis
PDB id:
Name: Complex (mhc protein/antigen)
Title: Hla-dr1 (dra, drb1 0101) human class ii histocompatibility protein (extracellular domain) complexed with endogenous peptide
Structure: Hla-dr1 class ii histocompatibility protein. Chain: a, d, g, j. Fragment: secreted extracellular domains. Synonym: dra, drb1 01010. Engineered: yes. Hla-dr1 class ii histocompatibility protein. Chain: b, e, h, k. Fragment: secreted extracellular domains. Synonym: dra, drb1 01010.
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: plasma. Tissue: lymphoid. Cellular_location: plasma membrane. Gene: dra 0101, Drb1 0101. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Hetero-Dimer (from PDB file)
2.45Å     R-factor:   0.216     R-free:   0.279
Authors: V.L.Murthy,L.J.Stern
Key ref:
V.L.Murthy and L.J.Stern (1997). The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding. Structure, 5, 1385-1396. PubMed id: 9351812 DOI: 10.1016/S0969-2126(97)00288-8
28-Jul-97     Release date:   28-Jan-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
254 a.a.
179 a.a.
Protein chains
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
266 a.a.
187 a.a.
Protein chains
Pfam   ArchSchema ?
P01892  (1A02_HUMAN) -  HLA class I histocompatibility antigen, A-2 alpha chain
365 a.a.
14 a.a.
Protein chain
Pfam   ArchSchema ?
P01892  (1A02_HUMAN) -  HLA class I histocompatibility antigen, A-2 alpha chain
365 a.a.
13 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


DOI no: 10.1016/S0969-2126(97)00288-8 Structure 5:1385-1396 (1997)
PubMed id: 9351812  
The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding.
V.L.Murthy, L.J.Stern.
BACKGROUND: Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions, although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide. RESULTS: The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins. CONCLUSIONS: The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1, an arginine residue at position +2, and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins.
  Selected figure(s)  
Figure 2.
Figure 2. Structure of the HLA-DR1-A2 peptide binding site. (a) Top view of the peptide-binding site, with HLA-DR1 residues in contact with the peptide indicated with sidechain or mainchain atoms as appropriate. Atoms are colored by atom type, with oxygen in red, nitrogen in blue and carbon atoms in green for the peptide and yellow for HLA-DR1. The peptide residues are numbered, with Trp(+1) in the principal binding pocket; hydrogen bonds are shown in magenta. (b) Schematic diagram of peptide hydrogen-bonding interactions. The peptide sidechains are shown as R[n] except for arginine at position 2 which contacts the HLA-DR1 mainchain carbonyl b77 at a kink in the b-chain helical region. The sidechain of His(+8) is also positioned to form a hydrogen bond with HLA-DR1 (not shown). The peptide mainchain is shaded in green. The interactions are color-coded: HLA-DR1-peptide hydrogen bonds, yellow; hydrogen bonds to buried water molecules, pink; hydrogen bonds to exposed water molecules, blue; Arg(+2) guanidinium-HLA-DR1 b77 carbonyl hydrogen bond, red. (c) Top view of the peptide-binding site, with the molecular surface indicated by blue dots. A Ca trace for HLA-DR1 is shown together with a stick model for the A2 peptide and buried water molecules; bonds are colored by atom type and water molecules are shown as spheres. Not all water molecules are observed in each molecule in the asymmetric unit.
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1385-1396) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
20066513 S.Sadegh-Nasseri, S.Natarajan, C.L.Chou, I.Z.Hartman, K.Narayan, and A.Kim (2010).
Conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection.
  Immunol Res, 47, 56-64.  
18767126 R.Yaneva, S.Springer, and M.Zacharias (2009).
Flexibility of the MHC class II peptide binding cleft in the bound, partially filled, and empty states: A molecular dynamics simulation study.
  Biopolymers, 91, 14-27.  
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.  
  19662225 J.M.Kneller, T.Ehlen, J.P.Matisic, D.Miller, D.Van Niekerk, W.L.Lam, M.Marra, R.Richards-Kortum, M.Follen, C.Macaulay, and S.J.Jones (2007).
Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling.
  Biomark Insights, 2, 447-461.  
17143275 K.Narayan, C.L.Chou, A.Kim, I.Z.Hartman, S.Dalai, S.Khoruzhenko, and S.Sadegh-Nasseri (2007).
HLA-DM targets the hydrogen bond between the histidine at position beta81 and peptide to dissociate HLA-DR-peptide complexes.
  Nat Immunol, 8, 92.  
17125142 A.Mangalam, M.Rodriguez, and C.David (2006).
Role of MHC class II expressing CD4+ T cells in proteolipid protein(91-110)-induced EAE in HLA-DR3 transgenic mice.
  Eur J Immunol, 36, 3356-3370.  
16426456 J.C.Tong, J.Bramson, D.Kanduc, S.Chow, A.A.Sinha, and S.Ranganathan (2006).
Modeling the bound conformation of Pemphigus vulgaris-associated peptides to MHC Class II DR and DQ alleles.
  Immunome Res, 2, 1.  
15598660 M.Srinivasan, D.Lu, R.Eri, D.D.Brand, A.Haque, and J.S.Blum (2005).
CD80 binding polyproline helical peptide inhibits T cell activation.
  J Biol Chem, 280, 10149-10155.  
16181330 T.H.Hansen, L.Lybarger, L.Yu, V.Mitaksov, and D.H.Fremont (2005).
Recognition of open conformers of classical MHC by chaperones and monoclonal antibodies.
  Immunol Rev, 207, 100-111.  
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.  
14757758 G.J.Carven, S.Chitta, I.Hilgert, M.M.Rushe, R.F.Baggio, M.Palmer, J.E.Arenas, J.L.Strominger, V.Horejsi, L.Santambrogio, and L.J.Stern (2004).
Monoclonal antibodies specific for the empty conformation of HLA-DR1 reveal aspects of the conformational change associated with peptide binding.
  J Biol Chem, 279, 16561-16570.  
15049778 K.Petersson, G.Forsberg, and B.Walse (2004).
Interplay between superantigens and immunoreceptors.
  Scand J Immunol, 59, 345-355.  
12913229 H.Nojima, M.Takeda-Shitaka, Y.Kurihara, K.Kamiya, and H.Umeyama (2003).
Dynamic flexibility of a peptide-binding groove of human HLA-DR1 class II MHC molecules: normal mode analysis of the antigen peptide-class II MHC complex.
  Chem Pharm Bull (Tokyo), 51, 923-928.  
  15208743 M.N.Davies, C.E.Sansom, C.Beazley, and D.S.Moss (2003).
A novel predictive technique for the MHC class II peptide-binding interaction.
  Mol Med, 9, 220-225.  
12767128 S.L.Lam, and V.L.Hsu (2003).
NMR identification of left-handed polyproline type II helices.
  Biopolymers, 69, 270-281.  
12952957 Z.Zavala-Ruiz, E.J.Sundberg, J.D.Stone, D.B.DeOliveira, I.C.Chan, J.Svendsen, R.A.Mariuzza, and L.J.Stern (2003).
Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1.
  J Biol Chem, 278, 44904-44912.
PDB code: 1pyw
11857638 B.J.McFarland, and C.Beeson (2002).
Binding interactions between peptides and proteins of the class II major histocompatibility complex.
  Med Res Rev, 22, 168-203.  
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.  
12399508 T.Areschoug, S.Linse, M.Stålhammar-Carlemalm, L.O.Hedén, and G.Lindahl (2002).
A proline-rich region with a highly periodic sequence in Streptococcal beta protein adopts the polyproline II structure and is exposed on the bacterial surface.
  J Bacteriol, 184, 6376-6383.  
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
11432818 K.Petersson, M.Håkansson, H.Nilsson, G.Forsberg, L.A.Svensson, A.Liljas, and B.Walse (2001).
Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence.
  EMBO J, 20, 3306-3312.
PDB code: 1hxy
11536359 O.Schueler-Furman, Y.Altuvia, and H.Margalit (2001).
Examination of possible structural constraints of MHC-binding peptides by assessment of their native structure within their source proteins.
  Proteins, 45, 47-54.  
10636922 A.K.Sato, J.A.Zarutskie, M.M.Rushe, A.Lomakin, S.K.Natarajan, S.Sadegh-Nasseri, G.B.Benedek, and L.J.Stern (2000).
Determinants of the peptide-induced conformational change in the human class II major histocompatibility complex protein HLA-DR1.
  J Biol Chem, 275, 2165-2173.  
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.  
10980449 J.R.Cochran, and L.J.Stern (2000).
A diverse set of oligomeric class II MHC-peptide complexes for probing T-cell receptor interactions.
  Chem Biol, 7, 683-696.  
10653650 P.M.Kasson, J.D.Rabinowitz, L.Schmitt, M.M.Davis, and H.M.McConnell (2000).
Kinetics of peptide binding to the class II MHC protein I-Ek.
  Biochemistry, 39, 1048-1058.  
11016975 R.R.Latek, S.J.Petzold, and E.R.Unanue (2000).
Hindering auxiliary anchors are potent modulators of peptide binding and selection by I-Ak class II molecules.
  Proc Natl Acad Sci U S A, 97, 11460-11465.  
10736175 R.V.Joshi, J.A.Zarutskie, and L.J.Stern (2000).
A three-step kinetic mechanism for peptide binding to MHC class II proteins.
  Biochemistry, 39, 3751-3762.  
10600129 B.J.McFarland, A.J.Sant, T.P.Lybrand, and C.Beeson (1999).
Ovalbumin(323-339) peptide binds to the major histocompatibility complex class II I-A(d) protein using two functionally distinct registers.
  Biochemistry, 38, 16663-16670.  
  10091661 B.J.Stapley, and T.P.Creamer (1999).
A survey of left-handed polyproline II helices.
  Protein Sci, 8, 587-595.  
10583947 E.L.Reinherz, K.Tan, L.Tang, P.Kern, J.Liu, Y.Xiong, R.E.Hussey, A.Smolyar, B.Hare, R.Zhang, A.Joachimiak, H.C.Chang, G.Wagner, and J.Wang (1999).
The crystal structure of a T cell receptor in complex with peptide and MHC class II.
  Science, 286, 1913-1921.
PDB code: 1d9k
10231540 J.A.Zarutskie, A.K.Sato, M.M.Rushe, I.C.Chan, A.Lomakin, G.B.Benedek, and L.J.Stern (1999).
A conformational change in the human major histocompatibility complex protein HLA-DR1 induced by peptide binding.
  Biochemistry, 38, 5878-5887.  
10607669 K.Maenaka, and E.Y.Jones (1999).
MHC superfamily structure and the immune system.
  Curr Opin Struct Biol, 9, 745-753.  
10229190 P.S.Andersen, P.M.Lavoie, R.P.Sékaly, H.Churchill, D.M.Kranz, P.M.Schlievert, K.Karjalainen, and R.A.Mariuzza (1999).
Role of the T cell receptor alpha chain in stabilizing TCR-superantigen-MHC class II complexes.
  Immunity, 10, 473-483.  
10631947 R.Wubbolts, and J.Neefjes (1999).
Intracellular transport and peptide loading of MHC class II molecules: regulation by chaperones and motors.
  Immunol Rev, 172, 189-208.  
9529149 C.A.Scott, P.A.Peterson, L.Teyton, and I.A.Wilson (1998).
Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be achieved without large anchor residues.
  Immunity, 8, 319-329.
PDB codes: 1iao 2iad
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