7S8F

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

7S8F の概要

• エントリーDOI: 10.2210/pdb7s8f/pdb
• 分子名称: HLA class I histocompatibility antigen, B-7 alpha chain, Beta-2-microglobulin, MLL cleavage product N320 peptide, ... (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, cancer, neoantigen
• 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: 45330.97

構造登録者

Patskovsky, Y.,Nyovanie, S.,Patskovska, L.,Natarajan, A.,Joshi, B.,Morin, B.,Brittsan, C.,Huber, O.,Gordon, S.,Michelet, X.,Schmitzberger, F.,Stein, R.,Findeis, M.,Hurwitz, A.,Van Dijk, M.,Buell, J.,Underwood, D.,Krogsgaard, M. (登録日: 2021-09-17, 公開日: 2022-11-02, 最終更新日: 2024-11-06)

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

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

実験手法

X-RAY DIFFRACTION (1.8 Å)