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7S8E

STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PHOSPHOPEPTIDE AND BOUND GLYCEROL

7S8E の概要
エントリーDOI10.2210/pdb7s8e/pdb
分子名称HLA class I histocompatibility antigen, B-7 alpha chain, Beta-2-microglobulin, MLL cleavage product N320 phosphopeptide, ... (5 entities in total)
機能のキーワードhla, mll peptide, mhc-i, hla-b*07:02, hla-b7, immunity, immune system, phosphopeptide, neoantigen, cancer
由来する生物種Homo sapiens (Human)
詳細
タンパク質・核酸の鎖数3
化学式量合計45595.14
構造登録者
主引用文献Patskovsky, Y.,Natarajan, A.,Patskovska, L.,Nyovanie, S.,Joshi, B.,Morin, B.,Brittsan, C.,Huber, O.,Gordon, S.,Michelet, X.,Schmitzberger, F.,Stein, R.B.,Findeis, M.A.,Hurwitz, A.,Van Dijk, M.,Chantzoura, E.,Yague, A.S.,Pollack Smith, D.,Buell, J.S.,Underwood, D.,Krogsgaard, M.
Molecular mechanism of phosphopeptide neoantigen immunogenicity.
Nat Commun, 14:3763-3763, 2023
Cited by
PubMed Abstract: 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 (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 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.
PubMed: 37353482
DOI: 10.1038/s41467-023-39425-1
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.6 Å)
構造検証レポート
Validation report summary of 7s8e
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-10-30に公開中

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