5e8n

The structure of the TEIPP associated Trh4 peptide in complex with H-2D(b)

spinqualitylabelsall models 5e8n, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5e8n is a 12 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4 Activity: Sphingosine N-acyltransferase, with EC number 2.3.1.24 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. [CERS5_MOUSE] Dihydroceramide synthase. Catalyzes the acylation of sphingosine to form dihydroceramide, with high selectivity toward palmitoyl-CoA as acyl donor compared to stearoyl-CoA. Inhibited by fumonisin B1. [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed MHC class I downregulation represents a significant challenge for successful T cell-based immunotherapy. T cell epitopes associated with impaired peptide processing (TEIPP) constitute a novel category of immunogenic Ags that are selectively presented on transporter associated with Ag processing-deficient cells. The TEIPP neoepitopes are CD8 T cell targets, derived from nonmutated self-proteins that might be exploited to prevent immune escape. In this study, the crystal structure of H-2Db in complex with the first identified TEIPP Ag (MCLRMTAVM) derived from the Trh4 protein has been determined to 2.25 A resolution. In contrast to prototypic H-2Db peptides, Trh4 takes a noncanonical peptide-binding pattern with extensive sulfur-pi interactions that contribute to the overall complex stability. Importantly, the noncanonical methionine at peptide position 5 acts as a main anchor, altering only the conformation of the H-2Db residues Y156 and H155 and thereby forming a unique MHC/peptide conformer that is essential for recognition by TEIPP-specific T cells. Substitution of peptide residues p2C and p5M to the conservative alpha-aminobutyric acid and norleucine, respectively, significantly reduced complex stability, without altering peptide conformation or T cell recognition. In contrast, substitution of p5M to a conventional asparagine abolished recognition by the H-2Db/Trh4-specific T cell clone LnB5. We anticipate that the H-2Db/Trh4 complex represents the first example, to our knowledge, of a broader repertoire of alternative MHC class I binders. The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer.,Hafstrand I, Doorduijn EM, Duru AD, Buratto J, Oliveira CC, Sandalova T, van Hall T, Achour A J Immunol. 2016 Jan 22. pii: 1502249. PMID:26800871 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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