5ks9

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Bel502-DQ8-glia-alpha1 complexBel502-DQ8-glia-alpha1 complex

Structural highlights

5ks9 is a 10 chain structure with sequence from Homo sapiens and Triticum aestivum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.55Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

L8E864_HUMAN

Publication Abstract from PubMed

In HLA-DQ8-associated celiac disease, TRAV26-2+-TRBV9+ and TRAV8-3+-TRBV6+ T cells recognize the immunodominant DQ8-glia-alpha1 epitope, whereupon a non-germline-encoded arginine residue played a key role in binding HLA-DQ8-glia-alpha1. Whether distinct T cell receptor (TCR) recognition modes exist for gliadin epitopes remains unclear. TCR repertoire analysis revealed populations of HLA-DQ8-glia-alpha1 and HLA-DQ8.5-glia-gamma1 restricted TRAV20+-TRBV9+ T cells that did not possess a non-germline-encoded arginine residue. The crystal structures of a TRAV20+-TRBV9+ TCR-HLA-DQ8-glia-alpha1 complex and two TRAV20+-TRBV9+ TCR-HLA-DQ8.5-glia-gamma1 complexes were determined. This revealed that the differential specificity toward DQ8-glia-alpha1 and DQ8.5-glia-gamma1 was governed by CDR3beta-loop-mediated interactions. Surprisingly, a germline-encoded arginine residue within the CDR1alpha loop of the TRAV20+ TCR substituted for the role of the non-germline-encoded arginine in the TRAV26-2+-TRBV9+ and TRAV8-3+-TRBV6+ TCRs. Thus, in celiac disease, the responding TCR repertoire is driven by a common mechanism that selects for structural elements within the TCR that have convergent binding solutions in HLA-DQ8-gliadin recognition.

Diverse T Cell Receptor Gene Usage in HLA-DQ8-Associated Celiac Disease Converges into a Consensus Binding Solution.,Petersen J, Kooy-Winkelaar Y, Loh KL, Tran M, van Bergen J, Koning F, Rossjohn J, Reid HH Structure. 2016 Aug 23. pii: S0969-2126(16)30221-0. doi:, 10.1016/j.str.2016.07.010. PMID:27568928[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Petersen J, Kooy-Winkelaar Y, Loh KL, Tran M, van Bergen J, Koning F, Rossjohn J, Reid HH. Diverse T Cell Receptor Gene Usage in HLA-DQ8-Associated Celiac Disease Converges into a Consensus Binding Solution. Structure. 2016 Aug 23. pii: S0969-2126(16)30221-0. doi:, 10.1016/j.str.2016.07.010. PMID:27568928 doi:http://dx.doi.org/10.1016/j.str.2016.07.010

5ks9, resolution 2.55Å

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