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PDBsum entry 1lek

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Immune system PDB id
1lek
Jmol
Contents
Protein chains
274 a.a. *
99 a.a. *
Ligands
GLU-GLN-TYR-LYS-
PHE-TYR-SER-VAL
NAG
NAG-NAG-FUC
PO4
Waters ×206
* Residue conservation analysis
PDB id:
1lek
Name: Immune system
Title: Crystal structure of h-2kbm3 bound to dev8
Structure: H-2 class i histocompatibility antigen, k-b alpha chain: a. Fragment: extracellular domain, sequence database residues numbered 1-274. Synonym: mhc class i h-2kb heavy chain. Engineered: yes. Beta-2-microglobulin. Chain: b. Fragment: sequence database residues 21-119, numbered 1-99.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide is chemically synthesized.
Biol. unit: Trimer (from PQS)
Resolution:
2.15Å     R-factor:   0.206     R-free:   0.258
Authors: J.G.Luz,M.Huang,K.C.Garcia,M.G.Rudolph,V.Apostolopoulos,L.Te I.A.Wilson
Key ref: J.G.Luz et al. (2002). Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) Interactions. J Exp Med, 195, 1175-1186. PubMed id: 11994422
Date:
09-Apr-02     Release date:   26-Jun-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01901  (HA1B_MOUSE) -  H-2 class I histocompatibility antigen, K-B alpha chain
Seq:
Struc:
369 a.a.
274 a.a.*
Protein chain
Pfam   ArchSchema ?
P01887  (B2MG_MOUSE) -  Beta-2-microglobulin
Seq:
Struc:
119 a.a.
99 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   10 terms 
  Biological process     immune system process   13 terms 
  Biochemical function     protein binding     3 terms  

 

 
J Exp Med 195:1175-1186 (2002)
PubMed id: 11994422  
 
 
Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) Interactions.
J.G.Luz, M.Huang, K.C.Garcia, M.G.Rudolph, V.Apostolopoulos, L.Teyton, I.A.Wilson.
 
  ABSTRACT  
 
The crystal structures of the 2C/H-2K(bm3)-dEV8 allogeneic complex at 2.4 A and H-2K(bm3)-dEV8 at 2.15 A, when compared with their syngeneic counterparts, elucidate structural changes that induce an alloresponse. The Asp77Ser mutation that imbues H-2K(bm3)-dEV8 with its alloreactive properties is located beneath the peptide and does not directly contact the T cell receptor (TCR). However, the buried mutation induces local rearrangement of the peptide itself to preserve hydrogen bonding interactions between the peptide and the alpha(1) 77 residue. The COOH terminus of the peptide main chain is tugged toward the alpha(1)-helix such that its presentation to the TCR is altered. These changes increase the stability of the allogeneic peptide-major histocompatibility complex (pMHC) complex and increase complementarity in the TCR-pMHC interface, placing greater emphasis on recognition of the pMHC by the TCR beta-chain, evinced by an increase in shape complementarity, buried surface area, and number of TCR-pMHC contacting residues. A nearly fourfold increase in the number of beta-chain-pMHC contacts is accompanied by a concomitant 64% increase in beta-chain-pMHC shape complementarity. Thus, the allogeneic mutation causes the same peptide to be presented differently, temporally and spatially, by the allogeneic and syngeneic MHCs.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22918468 A.K.Sewell (2012).
Why must T cells be cross-reactive?
  Nat Rev Immunol, 12, 669-677.  
22790179 O.P.Joffre, E.Segura, A.Savina, and S.Amigorena (2012).
Cross-presentation by dendritic cells.
  Nat Rev Immunol, 12, 557-569.  
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.  
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.  
  20948629 D.M.Kranz (2009).
Two mechanisms that account for major histocompatibility complex restriction of T cells.
  F1000 Biol Rep, 1, 0.  
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
  19177349 P.Kumar, A.Vahedi-Faridi, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2009).
Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity.
  Protein Sci, 18, 37-49.
PDB code: 3bo8
19617632 P.Kumar, A.Vahedi-Faridi, W.Saenger, E.Merino, J.A.López de Castro, B.Uchanska-Ziegler, and A.Ziegler (2009).
Structural basis for T cell alloreactivity among three HLA-B14 and HLA-B27 antigens.
  J Biol Chem, 284, 29784-29797.
PDB codes: 3bp4 3bp7 3bvn 3bxn
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.  
18726714 E.J.Collins, and D.S.Riddle (2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
  Immunol Res, 41, 267-294.  
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.  
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
18023633 A.Bharat, and T.Mohanakumar (2007).
Allopeptides and the alloimmune response.
  Cell Immunol, 248, 31-43.  
17485514 C.McCarthy, D.Shepherd, S.Fleire, V.S.Stronge, M.Koch, P.A.Illarionov, G.Bossi, M.Salio, G.Denkberg, F.Reddington, A.Tarlton, B.G.Reddy, R.R.Schmidt, Y.Reiter, G.M.Griffiths, P.A.van der Merwe, G.S.Besra, E.Y.Jones, F.D.Batista, and V.Cerundolo (2007).
The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation.
  J Exp Med, 204, 1131-1144.  
17418792 L.A.Colf, A.J.Bankovich, N.A.Hanick, N.A.Bowerman, L.L.Jones, D.M.Kranz, and K.C.Garcia (2007).
How a single T cell receptor recognizes both self and foreign MHC.
  Cell, 129, 135-146.
PDB codes: 2e7l 2oi9
17670943 L.Varani, A.J.Bankovich, C.W.Liu, L.A.Colf, L.L.Jones, D.M.Kranz, J.D.Puglisi, and K.C.Garcia (2007).
Solution mapping of T cell receptor docking footprints on peptide-MHC.
  Proc Natl Acad Sci U S A, 104, 13080-13085.  
18007679 N.J.Felix, and P.M.Allen (2007).
Specificity of T-cell alloreactivity.
  Nat Rev Immunol, 7, 942-953.  
16470819 A.J.Bordner, and R.Abagyan (2006).
Ab initio prediction of peptide-MHC binding geometry for diverse class I MHC allotypes.
  Proteins, 63, 512-526.  
16617112 L.K.Ely, T.Beddoe, C.S.Clements, J.M.Matthews, A.W.Purcell, L.Kjer-Nielsen, J.McCluskey, and J.Rossjohn (2006).
Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction.
  Proc Natl Acad Sci U S A, 103, 6641-6646.  
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.  
16297661 S.R.Burrows, J.Rossjohn, and J.McCluskey (2006).
Have we cut ourselves too short in mapping CTL epitopes?
  Trends Immunol, 27, 11-16.  
16275762 F.E.Tynan, D.Elhassen, A.W.Purcell, J.M.Burrows, N.A.Borg, J.J.Miles, N.A.Williamson, K.J.Green, J.Tellam, L.Kjer-Nielsen, J.McCluskey, J.Rossjohn, and S.R.Burrows (2005).
The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation.
  J Exp Med, 202, 1249-1260.
PDB codes: 2axf 2axg
16186824 F.E.Tynan, S.R.Burrows, A.M.Buckle, C.S.Clements, N.A.Borg, J.J.Miles, T.Beddoe, J.C.Whisstock, M.C.Wilce, S.L.Silins, J.M.Burrows, L.Kjer-Nielsen, L.Kostenko, A.W.Purcell, J.McCluskey, and J.Rossjohn (2005).
T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide.
  Nat Immunol, 6, 1114-1122.
PDB code: 2ak4
16260763 H.Li, S.Van Vranken, Y.Zhao, Z.Li, Y.Guo, L.Eisele, and Y.Li (2005).
Crystal structures of T cell receptor (beta) chains related to rheumatoid arthritis.
  Protein Sci, 14, 3025-3038.
PDB codes: 2axh 2axj
16267689 I.Belda, S.Madurga, X.Llorà, M.Martinell, T.Tarragó, M.G.Piqueras, E.Nicolás, and E.Giralt (2005).
ENPDA: an evolutionary structure-based de novo peptide design algorithm.
  J Comput Aided Mol Des, 19, 585-601.  
15837811 J.L.Chen, G.Stewart-Jones, G.Bossi, N.M.Lissin, L.Wooldridge, E.M.Choi, G.Held, P.R.Dunbar, R.M.Esnouf, M.Sami, J.M.Boulter, P.Rizkallah, C.Renner, A.Sewell, P.A.van der Merwe, B.K.Jakobsen, G.Griffiths, E.Y.Jones, and V.Cerundolo (2005).
Structural and kinetic basis for heightened immunogenicity of T cell vaccines.
  J Exp Med, 201, 1243-1255.
PDB codes: 2bnq 2bnr 2bnu
16046628 S.Madurga, I.Belda, X.Llorà, and E.Giralt (2005).
Design of enhanced agonists through the use of a new virtual screening method: application to peptides that bind class I major histocompatibility complex (MHC) molecules.
  Protein Sci, 14, 2069-2079.  
14734527 M.Hülsmeyer, M.T.Fiorillo, F.Bettosini, R.Sorrentino, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2004).
Dual, HLA-B27 subtype-dependent conformation of a self-peptide.
  J Exp Med, 199, 271-281.
PDB codes: 1of2 1ogt
15557346 M.J.Miley, I.Messaoudi, B.M.Metzner, Y.Wu, J.Nikolich-Zugich, and D.H.Fremont (2004).
Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution.
  J Exp Med, 200, 1445-1454.
PDB codes: 1rjy 1rjz 1rk0 1rk1
12848953 A.Pleister, and D.D.Eckels (2003).
Cryptic infection and autoimmunity.
  Autoimmun Rev, 2, 126-132.  
12909456 D.Housset, and B.Malissen (2003).
What do TCR-pMHC crystal structures teach us about MHC restriction and alloreactivity?
  Trends Immunol, 24, 429-437.  
12530975 L.Kjer-Nielsen, C.S.Clements, A.W.Purcell, A.G.Brooks, J.C.Whisstock, S.R.Burrows, J.McCluskey, and J.Rossjohn (2003).
A structural basis for the selection of dominant alphabeta T cell receptors in antiviral immunity.
  Immunity, 18, 53-64.
PDB code: 1mi5
12939341 W.A.Macdonald, A.W.Purcell, N.A.Mifsud, L.K.Ely, D.S.Williams, L.Chang, J.J.Gorman, C.S.Clements, L.Kjer-Nielsen, D.M.Koelle, S.R.Burrows, B.D.Tait, R.Holdsworth, A.G.Brooks, G.O.Lovrecz, L.Lu, J.Rossjohn, and J.McCluskey (2003).
A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition.
  J Exp Med, 198, 679-691.
PDB codes: 1m6o 1n2r
12394172 J.J.Molldrem, K.Komanduri, and E.Wieder (2002).
Overexpressed differentiation antigens as targets of graft-versus-leukemia reactions.
  Curr Opin Hematol, 9, 503-508.  
12152083 L.C.Wu, D.S.Tuot, D.S.Lyons, K.C.Garcia, and M.M.Davis (2002).
Two-step binding mechanism for T-cell receptor recognition of peptide MHC.
  Nature, 418, 552-556.  
12429093 L.Kjer-Nielsen, C.S.Clements, A.G.Brooks, A.W.Purcell, J.McCluskey, and J.Rossjohn (2002).
The 1.5 A crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance.
  Structure, 10, 1521-1532.
PDB code: 1kgc
12445302 M.Ramos, and J.A.López de Castro (2002).
HLA-B27 and the pathogenesis of spondyloarthritis.
  Tissue Antigens, 60, 191-205.  
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.