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PDBsum entry 1sys
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Immune system PDB id
1sys

 

 

 

 

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Contents
Protein chains
276 a.a. *
99 a.a. *
Ligands
GLU-GLU-PRO-THR-
VAL-ILE-LYS-LYS-
TYR
Waters ×186
* Residue conservation analysis
PDB id:
1sys
Name: Immune system
Title: Crystal structure of hla, b 4403, And peptide eeptvikky
Structure: Leukocyte antigen (hla) class i molecule. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: hdcma22p. Engineered: yes. Sorting nexin 5. Chain: c.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b, hlab. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: b2m. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
2.40Å     R-factor:   0.241     R-free:   0.271
Authors: D.Zernich,A.W.Purcell,W.A.Macdonald,L.Kjer-Nielsen,L.K.Ely,N.Laham, T.Crockford,N.A.Mifsud,B.D.Tait,R.Holdsworth,A.G.Brooks, S.P.Bottomley,T.Beddoe,C.A.Peh,J.Rossjohn,J.Mccluskey
Key ref: D.Zernich et al. (2004). Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion. J Exp Med, 200, 13-24. PubMed id: 15226359
Date:
01-Apr-04     Release date:   19-Oct-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens
Seq:
Struc: 		362 a.a.
276 a.a.*
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
99 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 31 residue positions (black crosses)

 

 
J Exp Med 200:13-24 (2004)
PubMed id: 15226359  
 
 
Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion.
D.Zernich, A.W.Purcell, W.A.Macdonald, L.Kjer-Nielsen, L.K.Ely, N.Laham, T.Crockford, N.A.Mifsud, M.Bharadwaj, L.Chang, B.D.Tait, R.Holdsworth, A.G.Brooks, S.P.Bottomley, T.Beddoe, C.A.Peh, J.Rossjohn, J.McCluskey.
 
  ABSTRACT  
 
HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20934997 C.Bade-Döding, A.Theodossis, S.Gras, L.Kjer-Nielsen, B.Eiz-Vesper, A.Seltsam, T.Huyton, J.Rossjohn, J.McCluskey, and R.Blasczyk (2011).
The impact of human leukocyte antigen (HLA) micropolymorphism on ligand specificity within the HLA-B*41 allotypic family.
  Haematologica, 96, 110-118.
PDB codes: 3ln4 3ln5
21387143 N.Vigneron, and B.J.Van den Eynde (2011).
Insights into the processing of MHC class I ligands gained from the study of human tumor epitopes.
  Cell Mol Life Sci, 68, 1503-1520.  
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.  
21050182 A.Van Hateren, E.James, A.Bailey, A.Phillips, N.Dalchau, and T.Elliott (2010).
The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding.
  Tissue Antigens, 76, 259-275.  
19687800 L.C.Simone, X.Wang, A.Tuli, and J.C.Solheim (2010).
Effect of a tapasin mutant on the assembly of the mouse MHC class I molecule H2-K(d).
  Immunol Cell Biol, 88, 57-62.  
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
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
19701894 N.Vigneron, D.R.Peaper, R.M.Leonhardt, and P.Cresswell (2009).
Functional significance of tapasin membrane association and disulfide linkage to ERp57 in MHC class I presentation.
  Eur J Immunol, 39, 2371-2376.  
19838694 V.Thammavongsa, M.Schaefer, T.Filzen, K.L.Collins, M.Carrington, N.Bangia, and M.Raghavan (2009).
Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503.
  Immunogenetics, 61, 703-716.  
20064448 W.A.Macdonald, Z.Chen, S.Gras, J.K.Archbold, F.E.Tynan, C.S.Clements, M.Bharadwaj, L.Kjer-Nielsen, P.M.Saunders, M.C.Wilce, F.Crawford, B.Stadinsky, D.Jackson, A.G.Brooks, A.W.Purcell, J.W.Kappler, S.R.Burrows, J.Rossjohn, and J.McCluskey (2009).
T cell allorecognition via molecular mimicry.
  Immunity, 31, 897-908.
PDB codes: 3kpl 3kpm 3kpn 3kpo 3kpp 3kpq 3kpr 3kps
18284468 A.N.Antoniou, and S.J.Powis (2008).
Pathogen evasion strategies for the major histocompatibility complex class I assembly pathway.
  Immunology, 124, 1.  
18452037 A.Tuli, M.Sharma, N.Naslavsky, S.Caplan, and J.C.Solheim (2008).
Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules.
  Immunogenetics, 60, 303-313.  
18243674 A.W.Purcell, and T.Elliott (2008).
Molecular machinations of the MHC-I peptide loading complex.
  Curr Opin Immunol, 20, 75-81.  
18240209 B.Galocha, and J.A.de Castro (2008).
Folding of HLA-B27 subtypes is determined by the global effect of polymorphic residues and shows incomplete correspondence to ankylosing spondylitis.
  Arthritis Rheum, 58, 401-412.  
18549801 D.Chessman, L.Kostenko, T.Lethborg, A.W.Purcell, N.A.Williamson, Z.Chen, L.Kjer-Nielsen, N.A.Mifsud, B.D.Tait, R.Holdsworth, C.A.Almeida, D.Nolan, W.A.Macdonald, J.K.Archbold, A.D.Kellerher, D.Marriott, S.Mallal, M.Bharadwaj, J.Rossjohn, and J.McCluskey (2008).
Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity.
  Immunity, 28, 822-832.
PDB code: 2rfx
18729726 D.R.Peaper, and P.Cresswell (2008).
Regulation of MHC class I assembly and peptide binding.
  Annu Rev Cell Dev Biol, 24, 343-368.  
18063114 L.Song, J.Le, F.Ye, H.Shao, H.J.Kaplan, and D.Sun (2008).
Sequence 168 to 177 of interphotoreceptor retinoid-binding protein (IRBP) is an antigenic epitope for autoreactive CD8 T cells in the B10RIII mouse.
  J Neuroimmunol, 193, 68-76.  
18489433 M.Marcilla, and J.A.López de Castro (2008).
Peptides: the cornerstone of HLA-B27 biology and pathogenetic role in spondyloarthritis.
  Tissue Antigens, 71, 495-506.  
18675588 M.Raghavan, N.Del Cid, S.M.Rizvi, and L.R.Peters (2008).
MHC class I assembly: out and about.
  Trends Immunol, 29, 436-443.  
18991276 N.Hillen, G.Mester, C.Lemmel, A.O.Weinzierl, M.Müller, D.Wernet, J.Hennenlotter, A.Stenzl, H.G.Rammensee, and S.Stevanović (2008).
Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA-B44 supertype.
  Eur J Immunol, 38, 2993-3003.  
17603488 A.Kienast, M.Preuss, M.Winkler, and T.P.Dick (2007).
Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin.
  Nat Immunol, 8, 864-872.  
17473845 A.W.Purcell, J.McCluskey, and J.Rossjohn (2007).
More than one reason to rethink the use of peptides in vaccine design.
  Nat Rev Drug Discov, 6, 404-414.  
17242432 F.Sieker, S.Springer, and M.Zacharias (2007).
Comparative molecular dynamics analysis of tapasin-dependent and -independent MHC class I alleles.
  Protein Sci, 16, 299-308.  
17853390 K.Daly, W.B.Church, K.Nicholas, and P.Williamson (2007).
Comparative modeling of marsupial MHC class I molecules identifies structural polymorphisms affecting functional motifs.
  J Exp Zool Part A Ecol Genet Physiol, 307, 611-624.  
17332746 M.Chen, and M.Bouvier (2007).
Analysis of interactions in a tapasin/class I complex provides a mechanism for peptide selection.
  EMBO J, 26, 1681-1690.  
16738940 D.H.Bos, and B.Waldman (2006).
Polymorphism, natural selection, and structural modeling of class Ia MHC in the African clawed frog (Xenopus laevis).
  Immunogenetics, 58, 433-442.  
16385505 J.C.Goodall, L.Ellis, and J.S.Hill Gaston (2006).
Spondylarthritis-associated and non-spondylarthritis-associated B27 subtypes differ in their dependence upon tapasin for surface expression and their incorporation into the peptide loading complex.
  Arthritis Rheum, 54, 138-147.  
15896200 C.Vilches, S.Sepúlveda, A.Balas, R.Solís, M.J.Avilés, E.Estefanía, N.Gómez-Lozano, J.L.Vicario, and R.dePablo (2005).
Complete coding sequences and haplotypic associations of HLA-B*0707, -B*1524, -B*4405, -B*4802, -DRB1*0409, -DRB1*0411, -DRB1*1115, -DRB1*1305, and the novel allele -DRB1*0709. Group-specific amplification of cDNA from DRB1 alleles associated to DRB3 and DRB4.
  Tissue Antigens, 65, 529-538.  
15653314 L.Lybarger, X.Wang, M.Harris, and T.H.Hansen (2005).
Viral immune evasion molecules attack the ER peptide-loading complex and exploit ER-associated degradation pathways.
  Curr Opin Immunol, 17, 71-78.  
16181328 N.Garbi, S.Tanaka, M.van den Broek, F.Momburg, and G.J.Hämmerling (2005).
Accessory molecules in the assembly of major histocompatibility complex class I/peptide complexes: how essential are they for CD8(+) T-cell immune responses?
  Immunol Rev, 207, 77-88.  
15609316 S.Oerke, H.Höhn, I.Zehbe, H.Pilch, K.H.Schicketanz, W.E.Hitzler, C.Neukirch, K.Freitag, and M.J.Maeurer (2005).
Naturally processed and HLA-B8-presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer.
  Int J Cancer, 114, 766-778.  
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.  
15493870 C.A.Wright, P.Kozik, M.Zacharias, and S.Springer (2004).
Tapasin and other chaperones: models of the MHC class I loading complex.
  Biol Chem, 385, 763-778.  
15342013 J.McCluskey, J.Rossjohn, and A.W.Purcell (2004).
TAP genes and immunity.
  Curr Opin Immunol, 16, 651-659.  
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.

 

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