3utp

1E6 TCR specific for HLA-A*0201-ALWGPDPAAA

spinqualitylabelsall models 3utp, resolution 2.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3utp is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.574Å Ligands: BTB, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The structural characteristics of the engagement of major histocompatibility complex (MHC) class II-restricted self antigens by autoreactive T cell antigen receptors (TCRs) is established, but how autoimmune TCRs interact with complexes of self peptide and MHC class I has been unclear. Here we examined how CD8(+) T cells kill human islet beta cells in type 1 diabetes via recognition of a human leukocyte antigen HLA-A*0201-restricted glucose-sensitive preproinsulin peptide by the autoreactive TCR 1E6. Rigid 'lock-and-key' binding underpinned the 1E6-HLA-A*0201-peptide interaction, whereby 1E6 docked similarly to most MHC class I-restricted TCRs. However, this interaction was extraordinarily weak because of limited contacts with MHC class I. TCR binding was highly peptide centric, dominated by two residues of the complementarity-determining region 3 (CDR3) loops that acted as an 'aromatic-cap' over the complex of peptide and MHC class I (pMHCI). Thus, highly focused peptide-centric interactions associated with suboptimal TCR-pMHCI binding affinities might lead to thymic escape and potential CD8(+) T cell-mediated autoreactivity. Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes.,Bulek AM, Cole DK, Skowera A, Dolton G, Gras S, Madura F, Fuller A, Miles JJ, Gostick E, Price DA, Drijfhout JW, Knight RR, Huang GC, Lissin N, Molloy PE, Wooldridge L, Jakobsen BK, Rossjohn J, Peakman M, Rizkallah PJ, Sewell AK Nat Immunol. 2012 Jan 15. doi: 10.1038/ni.2206. PMID:22245737 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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