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PDBsum entry 2p24

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protein Protein-protein interface(s) links
Immune system PDB id
2p24
Jmol
Contents
Protein chains
182 a.a. *
194 a.a. *
Waters ×206
* Residue conservation analysis
PDB id:
2p24
Name: Immune system
Title: I-au/mbp125-135
Structure: H-2 class ii histocompatibility antigen, a-u alph chain: a. Engineered: yes. H-2 class ii histocompatibility antigen, a-u beta chain: b. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: h2-aa. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Gene: i-au.
Resolution:
2.15Å     R-factor:   0.211     R-free:   0.260
Authors: C.Mcbeth,R.K.Strong
Key ref:
C.McBeth et al. (2008). A new twist in TCR diversity revealed by a forbidden alphabeta TCR. J Mol Biol, 375, 1306-1319. PubMed id: 18155234 DOI: 10.1016/j.jmb.2007.11.020
Date:
06-Mar-07     Release date:   15-Jan-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P14438  (HA2U_MOUSE) -  H-2 class II histocompatibility antigen, A-U alpha chain (Fragment)
Seq:
Struc:
227 a.a.
182 a.a.
Protein chain
No UniProt id for this chain
Struc: 194 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/j.jmb.2007.11.020 J Mol Biol 375:1306-1319 (2008)
PubMed id: 18155234  
 
 
A new twist in TCR diversity revealed by a forbidden alphabeta TCR.
C.McBeth, A.Seamons, J.C.Pizarro, S.J.Fleishman, D.Baker, T.Kortemme, J.M.Goverman, R.K.Strong.
 
  ABSTRACT  
 
We report crystal structures of a negatively selected T cell receptor (TCR) that recognizes two I-A(u)-restricted myelin basic protein peptides and one of its peptide/major histocompatibility complex (pMHC) ligands. Unusual complementarity-determining region (CDR) structural features revealed by our analyses identify a previously unrecognized mechanism by which the highly variable CDR3 regions define ligand specificity. In addition to the pMHC contact residues contributed by CDR3, the CDR3 residues buried deep within the V alpha/V beta interface exert indirect effects on recognition by influencing the V alpha/V beta interdomain angle. This phenomenon represents an additional mechanism for increasing the potential diversity of the TCR repertoire. Both the direct and indirect effects exerted by CDR residues can impact global TCR/MHC docking. Analysis of the available TCR structures in light of these results highlights the significance of the V alpha/V beta interdomain angle in determining specificity and indicates that TCR/pMHC interface features do not distinguish autoimmune from non-autoimmune class II-restricted TCRs.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Analysis of TCR/pMHC class II interfaces. (a) ΔΔG and footprint analyses of the interfaces of all six TCR/MHC II complexes currently available are mapped onto molecular surfaces of the TCR and pMHC from each complex, colored by domain (TCRα, light yellow; TCRβ, light orange; MHCα, dark blue; MHCβ, light blue; and peptide, green). Each complex has been splayed open to reveal interface features, with each partner in a complex viewed from the perspective of the cognate partner. For each complex pair, the TCR is shown above the MHC. Hotspot symbols (circles for TCR residues, squares for pMHC residues) are scaled to the magnitude of the contribution (ranging from 1 kcal/mol to 7 kcal/mol), labeled by residue ID and colored according to chain identity. For each surface, the footprint of the binding partner is outlined as an irregular blob, colored by the molecule contributing the contact: TCRα in yellow, TCRβ in orange, MHCα in dark blue, MHCβ in light blue and the peptide in green. (b) Overlay, based on MHC α-chain superpositions, of the minimum bounding rectangles for TCR footprints on pMHCs. Bounding boxes of TCR footprints from non-autoimmune contexts are shown in orange and those from autoimmune contexts are shown in green. The center of each box is indicated by a cross. (c) 1.D9.B2 experimental hotspots (Figure 1) are mapped onto the sc1.D9.B2 structure for comparison to the data above (molecular surface colored as in (a); residues where mutations abolish recognition of both ligands are shown as hotspot symbols colored as in (a)). The structure of the disordered CDR3β loop and the footprint of pMHC125 are based on the computationally docked model (Figure 6). Residues that are distal from the recognition surface are labeled in italics and residues on the recognition surface are labeled in boldface.
Figure 4.
Figure 4. Structure of pMHC125 alone and docked onto sc1.D9.B2. (a) Ribbon representations are shown of the structure of pMHC125 (viewed from the perspective of a TCR). Peptide residues that are available for TCR contact are shown in red, peptide residues occupying shallow surface pockets are shown in green, and peptide residues that serve as MHC anchors are shown in blue. (b) Structural comparison of MBPAc1-11 (gray) and MBP125-135 (green) when bound to I-A^u. (c) Computationally docked model of 1.D9.B2/pMHC125 complex using RosettaDock. MHC α and β chains are depicted in dark blue and light blue, respectively, with peptide residues in green. TCR chains are shown in yellow (α) and orange (β).
 
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 375, 1306-1319) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20462859 F.Lauck, C.A.Smith, G.F.Friedland, E.L.Humphris, and T.Kortemme (2010).
RosettaBackrub--a web server for flexible backbone protein structure modeling and design.
  Nucleic Acids Res, 38, W569-W575.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
19416894 K.Rubtsova, J.P.Scott-Browne, F.Crawford, S.Dai, P.Marrack, and J.W.Kappler (2009).
Many different Vbeta CDR3s can reveal the inherent MHC reactivity of germline-encoded TCR V regions.
  Proc Natl Acad Sci U S A, 106, 7951-7956.  
18962897 S.A.Richman, D.H.Aggen, M.L.Dossett, D.L.Donermeyer, P.M.Allen, P.D.Greenberg, and D.M.Kranz (2009).
Structural features of T cell receptor variable regions that enhance domain stability and enable expression as single-chain ValphaVbeta fragments.
  Mol Immunol, 46, 902-916.  
18726714 E.J.Collins, and D.S.Riddle (2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
  Immunol Res, 41, 267-294.  
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.  
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.