1FNE

HISTOCOMPATIBILITY ANTIGEN

Summary for 1FNE

• Entry DOI: 10.2210/pdb1fne/pdb
• Related: 1iea
• Descriptor: PROTEIN (MHC CLASS II I-EK, ALPHA CHAIN), PROTEIN (MHC CLASS II I-EK, BETA CHAIN), 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: histocompatibility antigen, mhc, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane ; Single-pass type I membrane protein : P04224
• Total number of polymer chains: 4
• Total formula weight: 96773.86

Authors

Miley, M.J.,Nelson, C.A.,Fremont, D.H. (deposition date: 2000-08-21, release date: 2001-03-07, Last modification date: 2023-08-09)

Primary citation

Kersh, G.J.,Miley, M.J.,Nelson, C.A.,Grakoui, A.,Horvath, S.,Donermeyer, D.L.,Kappler, J.,Allen, P.M.,Fremont, D.H.
Structural and functional consequences of altering a peptide MHC anchor residue.
J.Immunol., 166:3345-3354, 2001

PubMed Abstract: 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.

PubMed: 11207290

Experimental method

X-RAY DIFFRACTION (1.9 Å)