3VFN

crystal structure of HLA B*3508LPEP151A, HLA mutant Ala151

Summary for 3VFN

• Entry DOI: 10.2210/pdb3vfn/pdb
• Related: 1ZHK 1zhl 2ak4 3VFM 3VFO 3VFP 3VFR 3VFS 3VFT 3VFU 3VFV 3VFW
• Descriptor: MHC class I antigen, Beta-2-microglobulin, LPEP peptide from EBV, LPEPLPQGQLTAY, ... (4 entities in total)
• Functional Keywords: hla b*3508, epstein barr virus, tcr, t cell, immune system, antigen-presenting molecule
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P61769
• Total number of polymer chains: 3
• Total formula weight: 45072.94

Authors

Liu, Y.,Rossjohn, J.,Gras, S. (deposition date: 2012-01-10, release date: 2012-03-07, Last modification date: 2023-09-13)

Primary citation

Liu, Y.C.,Chen, Z.,Burrows, S.R.,Purcell, A.W.,McCluskey, J.,Rossjohn, J.,Gras, S.
The Energetic Basis Underpinning T-cell Receptor Recognition of a Super-bulged Peptide Bound to a Major Histocompatibility Complex Class I Molecule.
J.Biol.Chem., 287:12267-12276, 2012

PubMed Abstract: Although the major histocompatibility complex class I (MHC-I) molecules typically bind short peptide (p) fragments (8-10 amino acids in length), longer, "bulged" peptides are often be presented by MHC-I. Such bulged pMHC-I complexes represent challenges for T-cell receptor (TCR) ligation, although the general principles underscoring the interaction between TCRs and bulged pMHC-I complexes are unclear. To address this, we have explored the energetic basis of how an immunodominant TCR (termed SB27) binds to a 13-amino acid viral peptide (LPEPLPQGQLTAY) complexed to human leukocyte antigen (HLA) B*3508. Using the crystal structure of the SB27 TCR-HLA B*3508(LPEP) complex as a guide, we undertook a comprehensive alanine-scanning mutagenesis approach at the TCR-pMHC-I interface and examined the effect of the mutations by biophysical (affinity measurements) and cellular approaches (tetramer staining). Although the structural footprint on HLA B*3508 was small, the energetic footprint was even smaller in that only two HLA B*3508 residues were critical for the TCR interaction. Instead, the energetic basis of this TCR-pMHC-I interaction was attributed to peptide-mediated interactions in which the complementarity determining region 3α and germline-encoded complementarity determining region 1β loops of the SB27 TCR played the principal role. Our findings highlight the peptide-centricity of TCR ligation toward a bulged pMHC-I complex.

PubMed: 22343629
DOI: 10.1074/jbc.M112.344689

Experimental method

X-RAY DIFFRACTION (1.5 Å)