8YJ3

N17.1.2 recognition of NRAS neoantigens

8YJ3 の概要

• エントリーDOI: 10.2210/pdb8yj3/pdb
• 分子名称: tcr beta, tcr alpha (2 entities in total)
• 機能のキーワード: t cell receptor, p-mhc, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 205045.90

構造登録者

Wu, D.C.,Mariuzza, R.A. (登録日: 2024-02-29, 公開日: 2024-12-04)

主引用文献

Wu, D.,Yin, R.,Chen, G.,Ribeiro-Filho, H.V.,Cheung, M.,Robbins, P.F.,Mariuzza, R.A.,Pierce, B.G.
Structural characterization and AlphaFold modeling of human T cell receptor recognition of NRAS cancer neoantigens.
Sci Adv, 10:eadq6150-eadq6150, 2024

PubMed Abstract: T cell receptors (TCRs) that recognize cancer neoantigens are important for anticancer immune responses and immunotherapy. Understanding the structural basis of TCR recognition of neoantigens provides insights into their exquisite specificity and can enable design of optimized TCRs. We determined crystal structures of a human TCR in complex with NRAS Q61K and Q61R neoantigen peptides and HLA-A1 major histocompatibility complex (MHC), revealing the molecular underpinnings for dual recognition and specificity versus wild-type NRAS peptide. We then used multiple versions of AlphaFold to model the corresponding complex structures, given the challenge of immune recognition for such methods. One implementation of AlphaFold2 (TCRmodel2) with additional sampling was able to generate accurate models of the complexes, while AlphaFold3 also showed strong performance, although success was lower for other complexes. This study provides insights into TCR recognition of a shared cancer neoantigen as well as the utility and practical considerations for using AlphaFold to model TCR-peptide-MHC complexes.

PubMed: 39576860
DOI: 10.1126/sciadv.adq6150

実験手法

X-RAY DIFFRACTION (3.503 Å)