9ZCL

N17.3.2 NRASQ61K HLA A1 complex

Summary for 9ZCL

• Entry DOI: 10.2210/pdb9zcl/pdb
• Related: 9YW4
• Descriptor: ILE-LEU-ASP-THR-ALA-GLY-LYS-GLU-GLU-TYR, HLA class I histocompatibility antigen, Beta-2-microglobulin, ... (7 entities in total)
• Functional Keywords: n17.3.2 nrasq61k hla a1 complex, t cell receptor neoantigen, recognition of nras neoantigens, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 96382.54

Authors

Sharma, V.K.,Gallagher, D.T.,Mariuzza, R.A. (deposition date: 2025-11-23, release date: 2026-06-17, Last modification date: 2026-09-16)

Primary citation

Sharma, V.K.,Gallagher, D.T.,Saravanakumar, S.,Singh, P.,Pierce, B.G.,Mariuzza, R.A.
Structural basis for oligoclonal T cell recognition of a shared NRAS cancer neoantigen.
Structure, 34:1211-, 2026

PubMed Abstract: T cell receptors (TCRs) specific for cancer neoantigens are important for anti-tumor immunity and immunotherapy. To understand the structural basis for T cell recognition of cancer neoantigens, we studied oligoclonal TCRs from patients with melanoma that recognize a neoepitope arising from a driver mutation in NRAS (NRAS) presented by HLA-A1. Structures of these TCRs in unbound form and bound to NRAS-HLA-A1 revealed that they employ chemically distinct strategies and engagement modes to distinguish between mutant and wild-type NRAS. The structures explain how the NRAS mutation rendered a self-antigen visible to T cells. We additionally benchmarked AlphaFold-based modeling of these complexes, showing that predictive accuracy varies markedly across TCR-peptide-MHC targets. We found that conformational plasticity can dramatically impact complex assembly accuracy. These findings define the basis for TCR recognition of a cancer neoantigen and provide stringent tests for computational modeling of TCR-peptide-MHC interactions relevant to cancer immunotherapy.

PubMed: 42476141
DOI: 10.1016/j.str.2026.06.008

Experimental method

X-RAY DIFFRACTION (2.3 Å)