3VFW: Crystal Structure Of Hla B3508 Lpep-P10ala, Peptide Mutant P10-Ala

Citation:
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 3alpha and germline-encoded complementarity determining region 1beta loops of the SB27 TCR played the principal role. Our findings highlight the peptide-centricity of TCR ligation toward a bulged pMHC-I complex.
PDB ID: 3VFWDownload
MMDB ID: 97479
PDB Deposition Date: 2012/1/10
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3VFW: trimeric; determined by author and by software (PISA)
Molecular Components in 3VFW
Label Count Molecule
Proteins (3 molecules)
1
MHC Class I Antigen
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
1
Lpep Peptide From Ebv, P10a, Lpeplpqgqatay
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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