9GV6

Structure of TCR in complex with peptide-HLA

Summary for 9GV6

• Entry DOI: 10.2210/pdb9gv6/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Peptide, ... (6 entities in total)
• Functional Keywords: tcr, hla, mhc, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 189525.09

Authors

Karuppiah, V. (deposition date: 2024-09-23, release date: 2025-04-23, Last modification date: 2025-04-30)

Primary citation

Powell, T.,Karuppiah, V.,Shaikh, S.A.,Pengelly, R.,Mai, N.,Barnbrook, K.,Sharma, A.,Harper, S.,Ebner, M.,Creese, A.J.
Determining T-cell receptor binding orientation and Peptide-HLA interactions using cross-linking mass spectrometry.
J.Biol.Chem., 301:108445-108445, 2025

PubMed Abstract: T cell receptors (TCRs) recognize specific peptides presented by human leukocyte antigens (HLAs) on the surface of antigen-presenting cells and are involved in fighting pathogens and cancer surveillance. Canonical docking orientation of TCRs to their target peptide-HLAs (pHLAs) is essential for T cell activation, with reverse binding TCRs lacking functionality. TCR binding geometry and molecular interaction footprint with pHLAs are typically obtained by determining the crystal structure. Here, we describe the use of a cross-linking tandem mass spectrometry (XL-MS/MS) method to decipher the binding orientation of several TCRs to their target pHLAs. Cross-linking sites were localized to specific residues and their molecular interactions showed differentiation between TCRs binding in canonical or reverse orientations. Structural prediction and crystal structure determination of two TCR-pHLA complexes validated these findings. The XL-MS/MS method described herein offers a faster and simpler approach for elucidating TCR-pHLA binding orientation and interactions.

PubMed: 40154610
DOI: 10.1016/j.jbc.2025.108445

Experimental method

X-RAY DIFFRACTION (2.77 Å)