7s8i

PHOSPHOPEPTIDE-SPECIFIC LC13 TCR, MONOCLINIC CRYSTAL FORM

spinqualitylabelsall models 7s8i, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7s8i is a 2 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 1.66Å Ligands: CL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Altered protein phosphorylation in cancer cells often leads to surface presentation of phosphopeptide neoantigens. However, their role in cancer immunogenicity remains unclear. Here we describe a mechanism by which an HLA-B*0702-specific acute myeloid leukemia phosphoneoantigen, pMLL(747-755) (EPR(pS)PSHSM), is recognized by a cognate T cell receptor named TCR27, a candidate for cancer immunotherapy. We show that the replacement of phosphoserine P(4) with serine or phosphomimetics does not affect pMHC conformation or peptide-MHC affinity but abrogates TCR27-dependent T cell activation and weakens binding between TCR27 and pMHC. Here we describe the crystal structures for TCR27 and cognate pMHC, map of the interface produced by nuclear magnetic resonance, and a ternary complex generated using information-driven protein docking. Our data show that non-covalent interactions between the epitope phosphate group and TCR27 are crucial for TCR specificity. This study supports development of new treatment options for cancer patients through target expansion and TCR optimization. Molecular mechanism of phosphopeptide neoantigen immunogenicity.,Patskovsky Y, Natarajan A, Patskovska L, Nyovanie S, Joshi B, Morin B, Brittsan C, Huber O, Gordon S, Michelet X, Schmitzberger F, Stein RB, Findeis MA, Hurwitz A, Van Dijk M, Chantzoura E, Yague AS, Pollack Smith D, Buell JS, Underwood D, Krogsgaard M Nat Commun. 2023 Jun 23;14(1):3763. doi: 10.1038/s41467-023-39425-1. PMID:37353482 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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