spacer
spacer

PDBsum entry 2av7
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Immune system PDB id
2av7

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
275 a.a. *
100 a.a. *
Ligands
LEU-LEU-PHE-GLY-
TYR-PRO-VAL-TYR-
VAL ×2
GOL ×20
Waters ×696
* Residue conservation analysis
PDB id:
2av7
Name: Immune system
Title: Crystal structure of htlv-1 tax peptide bound to human class i mhc hla-a2 with the k66a mutation in the heavy chain.
Structure: Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a, d. Synonym: mhc class i antigen a 2. Engineered: yes. Mutation: yes. Beta-2-microglobulin. Chain: b, e. Engineered: yes. Trans-activating transcriptional regulatory peptide.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a, hlaa. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: b2m. Synthetic: yes. Human t-cell leukemia virus 1 (isolate caribbea
Biol. unit: Trimer (from PQS)
Resolution:
2.05Å     R-factor:   0.175     R-free:   0.234
Authors: O.Y.Borbulevych,B.M.Baker
Key ref:
S.J.Gagnon et al. (2005). Unraveling a hotspot for TCR recognition on HLA-A2: evidence against the existence of peptide-independent TCR binding determinants. J Mol Biol, 353, 556-573. PubMed id: 16197958 DOI: 10.1016/j.jmb.2005.08.024
Date:
29-Aug-05     Release date:   18-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens
Seq:
Struc: 		365 a.a.
275 a.a.*
Protein chains
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 20 residue positions (black crosses)

 

 
DOI no: 10.1016/j.jmb.2005.08.024 J Mol Biol 353:556-573 (2005)
PubMed id: 16197958  
 
 
Unraveling a hotspot for TCR recognition on HLA-A2: evidence against the existence of peptide-independent TCR binding determinants.
S.J.Gagnon, O.Y.Borbulevych, R.L.Davis-Harrison, T.K.Baxter, J.R.Clemens, K.M.Armstrong, R.V.Turner, M.Damirjian, W.E.Biddison, B.M.Baker.
 
  ABSTRACT  
 
T cell receptor (TCR) recognition of peptide takes place in the context of the major histocompatibility complex (MHC) molecule, which accounts for approximately two-thirds of the peptide/MHC buried surface. Using the class I MHC HLA-A2 and a large panel of mutants, we have previously shown that surface mutations that disrupt TCR recognition vary with the identity of the peptide. The single exception is Lys66 on the HLA-A2 alpha1 helix, which when mutated to alanine disrupts recognition for 93% of over 250 different T cell clones or lines, independent of which peptide is bound. Thus, Lys66 could serve as a peptide-independent TCR binding determinant. Here, we have examined the role of Lys66 in TCR recognition of HLA-A2 in detail. The structure of a peptide/HLA-A2 molecule with the K66A mutation indicates that although the mutation induces no major structural changes, it results in the exposure of a negatively charged glutamate (Glu63) underneath Lys66. Concurrent replacement of Glu63 with glutamine restores TCR binding and function for T cells specific for five different peptides presented by HLA-A2. Thus, the positive charge on Lys66 does not serve to guide all TCRs onto the HLA-A2 molecule in a manner required for productive signaling. Furthermore, electrostatic calculations indicate that Lys66 does not contribute to the stability of two TCR-peptide/HLA-A2 complexes. Our findings are consistent with the notion that each TCR arrives at a unique solution of how to bind a peptide/MHC, most strongly influenced by the chemical and structural features of the bound peptide. This would not rule out an intrinsic affinity of TCRs for MHC molecules achieved through multiple weak interactions, but for HLA-A2 the collective mutational data place limits on the role of any single MHC amino acid side-chain in driving TCR binding in a peptide-independent fashion.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The conformation of the Tax peptide in the K66A, E63Q/K66A, and wild-type Tax/HLA-A2 structures is identical. (a) and (b) 2F[o] -F[c] peptide densities contoured at 1s for the (a) K66A and (b) E63Q/K66A structures. (c) Superimposition of the Tax peptide from the K66A, E63Q/K66A, and wild-type structures. K66A is yellow, E63Q/K66A is white, and wild-type is blue. 		Figure 5.
Figure 5. Effects of the K66A and E63Q/K66A mutations on electrostatic surface potentials. (a) Electrostatic potential on the surface of wild-type Tax/HLA-A2. The circled region, enlarged on the right-hand side, is characterized by a positive surface potential. (b) The K66A mutation reverses the potential at this position. (c) The E63Q/K66A double mutation results in a surface potential close to neutrality. The scale, from red to blue, is -5 to +5kT/e.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 353, 556-573) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
18275829 J.Ishizuka, G.B.Stewart-Jones, A.van der Merwe, J.I.Bell, A.J.McMichael, and E.Y.Jones (2008).
The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain.
  Immunity, 28, 171-182.
PDB codes: 2vlj 2vlk 2vll 2vlm 2vlr
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.  
18973345 L.L.Jones, L.A.Colf, A.J.Bankovich, J.D.Stone, Y.G.Gao, C.M.Chan, R.H.Huang, K.C.Garcia, and D.M.Kranz (2008).
Different thermodynamic binding mechanisms and peptide fine specificities associated with a panel of structurally similar high-affinity T cell receptors.
  Biochemistry, 47, 12398-12408.
PDB code: 3ery
  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
17521918 C.Mazza, and B.Malissen (2007).
What guides MHC-restricted TCR recognition?
  Semin Immunol, 19, 225-235.  
17493154 H.Abdeen, C.McErlean, M.E.Moraes, M.Romero, S.B.Marques, A.C.Goncales, E.G.Guariento, and D.Middleton (2007).
Identification of two novel alleles HLA-B*3569 and -B*4450 and confirmation of HLA-A*2631 in the Brazilian population.
  Tissue Antigens, 69, 273-276.  
17825839 P.J.Miller, Y.Pazy, B.Conti, D.Riddle, E.Appella, and E.J.Collins (2007).
Single MHC mutation eliminates enthalpy associated with T cell receptor binding.
  J Mol Biol, 373, 315-327.
PDB codes: 2j8u 2jcc 2uwe
17041605 E.S.Huseby, F.Crawford, J.White, P.Marrack, and J.W.Kappler (2006).
Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide.
  Nat Immunol, 7, 1191-1199.  
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 codes are shown on the right.

 

spacer
spacer