1fng

OverviewOverview

To better understand TCR discrimination of multiple ligands, we have, analyzed the crystal structures of two Hb peptide/I-E(k) complexes that, differ by only a single amino acid substitution at the P6 anchor position, within the peptide (E73D). Detailed comparison of multiple independently, determined structures at 1.9 A resolution reveals that removal of a single, buried methylene group can alter a critical portion of the TCR recognition, surface. Significant variance was observed in the peptide P5-P8 main chain, as well as a rotamer difference at LeuP8, approximately 10 A distal from, the substitution. No significant variations were observed in the, conformation of the two MHC class II molecules. The ligand alteration, results in two peptide/MHC complexes that generate bulk T cell responses, that are distinct and essentially nonoverlapping. For the Hb-specific T, cell 3.L2, substitution reduces the potency of the ligand 1000-fold., Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar, affinity, although with faster kinetics. These results highlight the role, of subtle variations in MHC Ag presentation on T cell activation and, signaling.

About this StructureAbout this Structure

1FNG is a Protein complex structure of sequences from Mus musculus with NAG as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Structural and functional consequences of altering a peptide MHC anchor residue., Kersh GJ, Miley MJ, Nelson CA, Grakoui A, Horvath S, Donermeyer DL, Kappler J, Allen PM, Fremont DH, J Immunol. 2001 Mar 1;166(5):3345-54. PMID:11207290

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